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Doxycycline (EENT)

Class: Antibacterials
Chemical Name: 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride
Molecular Formula: (C22H24N2O8•HCl)2
CAS Number: 24390-14-5
Brands: Atridox

Medically reviewed by Last updated on May 4, 2020.


Antibacterial; tetracycline antibiotic.1 14

Uses for Doxycycline (EENT)


Used orally for treatment of adult periodontitis as an adjunct to scaling and root planing to promote attachment-level gain and reduce pocket depth.14 15 16

Used subgingivally for treatment of chronic adult periodontitis to reduce pocket depth, gain clinical attachment level, and reduce bleeding associated with probing.1 2 3 4 5 7 10 11

Doxycycline (EENT) Dosage and Administration


Oral Administration

Administered orally as 20-mg tablets for adjunctive treatment of periodontitis.14

Take twice daily at least 1 hour prior to or 2 hours after meals.14

Give with adequate amounts of fluids to reduce risk of esophageal irritation and ulceration.14

Subgingival Administration

Administered subgingivally as an extended-release preparation into periodontal pockets by a dental health-care professional.1

Commercially available as a kit containing a syringe of a liquid polymeric delivery system (syringe A), a syringe of doxycycline (syringe B), and a blunt cannula.1 Contents of the 2 syringes must be mixed together prior to administration.1 (See Reconstitution under Dosage and Administration.)

Final mixture appears as a pale yellow to yellow viscous liquid;1 after subgingival administration into periodontal pockets, the liquid solidifies to provide controlled release of doxycycline over a period of 7 days.1 8

Each pair of syringes is intended for single use only.1

Administration does not require local anesthesia.1

Extended-release preparation is bioabsorbed or expelled naturally and does not need to be manually removed.1


Mix contents of the 2 paired syringes (liquid polymeric delivery system [syringe A] and doxycycline powder [syringe B]) together prior to administration.1

Remove syringes from the refrigerator at least 15 minutes prior to mixing.1

Couple syringes together and inject contents of syringe A into syringe B and then back into syringe A to complete 1 mixing cycle.1 Perform a total of 100 mixing cycles using brisk strokes (approximately 1 mixing cycle per second).1

If not administered immediately, coupled syringes may be stored in resealable pouch (or airtight container) at room temperature for up to 3 days.1 After such storage, perform an additional 10 mixing cycles prior to administration.1

After mixing, hold coupled syringes vertically with syringe A (indicated by a red stripe) at the bottom.1 Pull down on plunger of syringe A and allow contents to flow down the barrel for several seconds into syringe A.1 Uncouple syringes and attach the blunt cannula supplied in the kit to syringe A.1 Bend cannula to resemble a periodontal probe.1

Subgingival Administration Technique

Using the syringe with bent cannula, position tip of cannula near base of the periodontal pocket and administer doxycycline polymer preparation into the pocket until mixture reaches the top of the gingival margin.1 Withdraw cannula from the pocket.1

If desired, the preparation may be packed into the periodontal pocket using an appropriate dental instrument.1 Dip edge of the dental instrument in water before packing to prevent the preparation from sticking to the instrument and to speed coagulation of the polymer.1 Once the preparation is in the periodontal pocket, drip a few drops of water onto its surface to aid in coagulation of the polymer.1 If necessary, add more doxycycline polymer and pack it into periodontal pocket until full.1

After subgingival administration is completed, cover pocket with periodontal dressing (Coe-Pak) or cyanoacrylate dental adhesive.1

Consult manufacturer’s literature for additional information on preparation and subgingival administration of doxycycline polymer.1


Available as doxycycline hyclate; dosage expressed in terms of doxycycline.1 14

Doxycycline hyclate polymer for subgingival administration: When prepared as directed (see Reconstitution under Dosage and Administration), mixture in the syringe contains 50 mg of doxycycline hyclate (equivalent to 42.5 mg of doxycycline).1



20 mg every 12 hours (morning and evening).14

Safety of >12 months of treatment and efficacy of >9 months of treatment not established.14


Dosage varies depending on the size, shape, and number of periodontal pockets treated.1

May repeat treatment 4 months after initial treatment.1

Cautions for Doxycycline (EENT)


  • Known hypersensitivity to doxycycline or other tetracyclines.1 14



Dental and Bone Effects

Do not use tetracyclines during tooth development (e.g., pregnancy, infancy, childhood up to 8 years of age); potential for permanent tooth discoloration (yellow-gray-brown) or enamel hypoplasia.1 14 Most common with long-term tetracycline use, but also reported following repeated short-term use.1 14

Tetracyclines form a stable calcium complex in any bone-forming tissue.14 Reversible decrease in fibula growth rate has occurred in premature infants receiving oral tetracycline.14

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, anaphylactoid purpura, serum sickness, urticaria, angioedema, pericarditis, and exacerbation of systemic lupus erythematosus, reported in patients receiving tetracyclines.14

Photosensitivity Reactions

Photosensitivity, manifested as exaggerated sunburn reaction on areas of body exposed to direct sunlight or ultraviolet (UV) light, reported in some patients receiving tetracyclines.1 14

Discontinue oral or subgingival doxycycline at first sign of skin erythema.13 14

Other Warnings/Precautions

Precautions Related to Oral Doxycycline

Oral dosage used in adjunctive treatment of periodontitis differs from that used for treatment of infections.14 An increased incidence of adverse effects, including development of resistant organisms, may occur if higher than recommended dosage used in patients with periodontitis.14

Oral dosage used in adjunctive treatment of periodontitis does not provide drug concentrations high enough to inhibit organisms commonly associated with adult periodontitis.14 The 20-mg tablets used in treatment of periodontitis should not be used in an attempt to reduce or eliminate such organisms.14

Precautions Related to Subgingival Doxycycline

Not studied in patients with extremely severe periodontal defects with little remaining periodontium.1

Not studied for use in the regeneration of alveolar bone, either in preparation for or in conjunction with placement of endosseous (dental) implants or in the treatment of failing implants.1

Not studied in immunocompromised patients (e.g., those with diabetes mellitus or HIV infection, those receiving chemotherapy or radiation therapy).1


Possible overgrowth of nonsusceptible organisms, including fungi, in patients receiving oral or subgingival doxycycline.1 14

Overgrowth of opportunistic microorganisms, such as yeast, not reported in clinical studies evaluating oral doxycycline in adults with periodontitis.14

Tetracyclines may increase the incidence of vaginal candidiasis.14

Use oral or subgingival doxycycline with caution in patients with a history of or predisposition to oral candidiasis.1 14 Safety and efficacy not established in patients with concomitant oral candidiasis.1 14

Specific Populations


Do not use tetracyclines during pregnancy.1 14 If a tetracycline used during pregnancy, apprise patient of potential hazards to the fetus.1 14

Can cause fetal harm if administered to pregnant women;14 effects of tetracyclines on labor and delivery unknown.14

Subgingival doxycycline not evaluated in pregnant women.1


Tetracyclines distributed into milk following oral administration.1 14 Not known whether doxycycline distributed into milk following subgingival administration.1

Doxycycline is contraindicated in nursing women.14 Discontinue nursing or the drug.1 14

Pediatric Use

Oral: Do not use in children <8 years of age.14 (See Dental and Bone Effects under Cautions.)

Subgingival: Safety and efficacy not established in pediatric patients <18 years of age.1 2 13

Common Adverse Effects

Oral: Headache, common cold, flu symptoms, toothache, GI symptoms (diarrhea, nausea, dyspepsia), joint pain.14

Subgingival: Headache; common cold; gum discomfort, pain or soreness, loss of attachment, or increased pocket depth; toothache or pressure sensitivity; periodontal abscess, exudate, infection, drainage, extreme mobility, or suppuration; thermal tooth sensitivity.1

Interactions for Doxycycline (EENT)

Drug interactions reported involve oral doxycycline.14 No formal drug interaction studies performed with subgingival doxycycline.1

Specific Drugs




Antacids (aluminum-, calcium-, or magnesium-containing)

Decreased doxycycline absorption14

Anticoagulants, oral

Possible decreased prothrombin activity14

Adjust anticoagulant dosage as needed14

Anticonvulsants (barbiturates, carbamazepine, phenytoin)

Possible decreased doxycycline half-life14

Bismuth subsalicylate

Possible decreased doxycycline absorption14

Hormonal contraceptives

Possible decreased effectiveness of oral contraceptives1 14

Iron-containing preparations

Possible decreased doxycycline absorption14


Fatal renal toxicity reported with concomitant use of tetracycline and methoxyflurane14


Possible antagonism14

Avoid concomitant use14

Doxycycline (EENT) Pharmacokinetics



Oral: Doxycycline hyclate rapidly and almost completely absorbed from GI tract.14 In adults receiving 20-mg tablets of doxycycline, peak serum doxycycline concentrations attained within 1.4 hours after a single dose or within 2 hours of a dose at steady state.14 Rate and extent of absorption decreased if doxycycline administered with a high-fat, high-protein meal that includes dairy products.14

Subgingival: Following administration of doxycycline hyclate polymer into periodontal pocket, mixture solidifies and provides controlled release of the drug for 7 days.1 8 Concentrations in gingival crevicular fluid (GCF) peaked 2 hours following subgingival administration and remained >1 mg/mL through 18 hours.1 GCF concentrations then declined gradually, but remained above MIC90 for periodontal pathogens (6 mcg/mL) through 7 days.1 Serum concentrations never exceeded 0.1 mcg/mL.1





20–25°C in tight, light-resistant container.14


For liquid, extended-release polymer


Actions and Spectrum

  • Mechanism of action of oral doxycycline in promoting attachment-level gain and reducing pocket depth in patients with adult periodontitis not elucidated.14 Although clinical importance unknown, doxycycline inhibits collagenase activity in vitro and oral doxycycline has reduced elevated collagenase activity in GCF of patients with adult periodontitis.14

  • Bacteriostatic.1 Inhibits protein synthesis in susceptible bacteria through disruption of transfer RNA and messenger RNA at ribosomal sites.1

  • Active in vitro against some organisms associated with periodontal disease.1

  • Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum are inhibited in vitro by doxycycline concentrations ≤6 mcg/mL.1

  • In one study, there was no evidence of emergence of doxycycline resistance in anaerobic flora cultured from subgingival plaque or saliva of adults with periodontitis who were treated with subgingival doxycycline.6

Advice to Patients

  • Advise patients taking doxycycline tablets of the importance of drinking sufficient amounts of fluids to reduce the risk of esophageal irritation and ulceration.14

  • Advise patients being treated with subgingival doxycycline of the importance of not using mechanical oral hygiene procedures (i.e., brushing teeth, flossing) around treated sites for 7 days after receiving subgingival doxycycline.1

  • Advise patients receiving oral or subgingival doxycycline of the importance of avoiding exposure to direct sunlight or UV light and importance of notifying a dental health-care professional and discontinuing therapy at the first sign of skin erythema.1 13 14

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.1 14

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 14 Advise patients that doxycycline may decrease effectiveness of oral contraceptives.1 14

  • Importance of informing patients of other important precautionary information.1 14 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Doxycycline Hyclate


Dosage Forms


Brand Names



Tablets, film-coated

20 mg (of doxycycline)*

Doxycycline Hyclate Tablets


Kit for liquid, extended-release polymer

Liquid for subgingival use, 450 mg of Atrigel polymeric controlled-release delivery system

Powder for subgingival use, 42.5 mg (of doxycycline)



AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 14, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. Den-Mat Holdings, LLC. Atridox (doxycycline hyclate 10%) prescribing information. Lompoc, CA; 2016 Oct.

2. Wennström JL, Newman HN, MacNeill SR et al. Utilisation of locally delivered doxycycline in non-surgical treatment of chronic periodontitis. J Clin Periodontol. 2001; 28:753-761.

3. Garrett S, Adams DF, Bogle G et al. The effect of locally delivered controlled-release doxycycline or scaling and root planing on periodontal maintenance patients over 9 months. J Periodontol. 2000; 71:22-30.

4. Garrett S, Johnson L, Drisko CH et al. Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis. J Periodontol. 1999; 70:490-503.

5. Drisko CH. The use of locally-delivered doxycycline in the treatment of periodontitis. Clinical results. J Clin Periodontol. 1998; 25:947-52.

6. Walker CB, Godowski KC, Borden L. The effects of sustained release doxycycline on anaerobic flora and antibiotic-resistant patterns in subgingival plaque and saliva. J Periodontol. 2000; 71:768-74.

7. Wolinsky LE, Camargo PM, Polson A et al. The significance of prior mechanical therapy for changes of periodontal status achieved by local delivery of a doxycycline-hyclate containing gel. J Clin Periodontol. 2001; 28:1115-20.

8. Stoller NH, Johnson LR, Trapnell S et al. The pharmacokinetic profile of a biodegradable controlled-release delivery system containing doxycycline compared to systemically delivered doxycycline in gingival crevicular fluid, saliva, and serum. J Periodontol. 1998; 69:1085-91.

9. Ryder MI, Pons B, Adams D et al. Effects of smoking on local delivery of controlled-release doxycycline as compared to scaling and root planing. J Clin Periodontol. 1999; 26:683-91.

10. Greenstein G, Tonetti M and the Research, Science, and Therapy Committee of the American Academy of Periodontology. Position Paper. The role of controlled drug delivery for periodontitis. J Periodontol. 2000; 71:125-40.

11. Greenstein G, Polson A. The role of local drug delivery in the management of periodontal diseases: a comprehensive review. J Periodontol. 1998; 69:507-520.

12. Garrett S. Local delivery of doxycycline for the treatment of periodontitis. Compendium. 1999; 20:437-46.

13. CollaGenex Pharmaceuticals, Inc. Newtown, PA; Personal communication.

14. Lannett Company, Inc. Doxycycline hyclate tablets (equivalent to 20 mg doxycycline) prescribing information. Philadelphia, PA; 2017 Aug.

15. Greenstein G. The role of Periostat in the management of adult periodontitis: a critical assessment. Compend Contin Educ Dent. 1999; 20:664,666-8,670,672,574,676-8.

16. Caton JG. Evaluation of Periostat for patient management. Compend Contin Educ Dent. 1999; 20:451-2,454-6,458-63.

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