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Doxycycline Hyclate 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, Periostat


Semisynthetic tetracycline antibiotic.1

Uses for Doxycycline Hyclate


Used orally as an adjunct to scaling and root planing to promote attachment-level gain and to reduce pocket depth in adults with periodontitis.14 15 16

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

Doxycycline Hyclate Dosage and Administration


Oral Administration

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

Administer doses in the morning and evening and 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 containing the drug incorporated into a bioresorbable polymer) into periodontal pockets by an oral health-care professional.1 4 10 11

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

Administration does not require local anesthesia.1

Preparation does not have to be manually removed; preparation solidifies upon contact with gingival crevicular fluid and is bioabsorbed or expelled naturally.1


Mix contents of the 2 paired syringes (liquid polymeric delivery system [syringe A]; doxycycline hyclate 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 100 mixing cycles (approximately 1 mixing cycle per second) prior to administration.1

If not administered immediately, store coupled syringes in resealable pouch at room temperature for up to 3 days; an additional 10 mixing cycles is required just prior to administration.1

After mixing, hold coupled syringes vertically with syringe A (indicated by a purple stripe) at the bottom.1 Pull down on the 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 package to syringe A prior to administration.1 Bend cannula to resemble a periodontal probe.1

Subgingival Administration Technique

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

After administration is completed, withdraw cannula from the pocket and cover pocket with periodontal dressing or dental adhesive.1


Available as doxycycline hyclate; dosage expressed in terms of doxycycline; 50 mg of doxycycline hyclate equivalent to 42.5 mg of doxycycline.1



20 mg every 12 hours.14

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


Dosage varies depending on the size, shape, and number of periodontal pockets treated.1 May repeat treatment 4 months after the initial treatment.1

Cautions for Doxycycline Hyclate


  • Known hypersensitivity to doxycycline or other tetracyclines.1 14



Dental and Bone Effects

Avoid use during tooth development (e.g., the last half of pregnancy, infancy, childhood up to 8 years of age); potential for permanent tooth discoloration or enamel hypoplasia.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

Photosensitivity Reactions

Possible photosensitivity reactions (e.g., exaggerated sunburn reaction).1 14 Discontinue oral or subgingival therapy at the first sign of skin erythema.13 14

General Precautions

Precautions Related to Subgingival Doxycycline

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 patients with extremely severe periodontal defects with little remaining periodontium.1

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

Oral Candidiasis

Possible overgrowth of nonsusceptible organisms, including fungi.1 14 Use 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


Category D.1 14


Distributed into milk.1 14 Discontinue nursing or the drug.1 14

Pediatric Use

Do not use oral doxycycline in children <8 years of age.14

Safety and efficacy of subgingival doxycycline not established in children <18 years of age.1 2 13

Possible permanent tooth discoloration (see Dental and Bone Effects under Cautions).1

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 Hyclate

Drug interactions reported involve oral doxycycline.14 No formal drug interaction studies have been performed with doxycycline hyclate polymer for subgingival administration.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 Hyclate Pharmacokinetics



Oral: Doxycycline hyclate rapidly and almost completely absorbed from GI tract.14 In adults receiving 20-mg tablets of doxycycline hyclate, peak serum doxycycline concentrations attained within 1.4 hours after a single dose or within 2 hours of a dose at steady-state.14

Subgingival: Concentrations in gingival crevicular fluid (GCF) peaked 2 hours following administration and remained >1000 mcg/mL through 18 hours.1 GCF concentrations then declined gradually but remained >MIC for periodontal pathogens (≤6 mcg/mL) through 7 days; serum concentrations remained ≤0.1 mcg/mL.1





15–30°C in tight, light-resistant container.14


For liquid, extended-release polymer


Actions and Spectrum

  • Usually is bacteriostatic.1

  • Inhibits protein synthesis in susceptible organisms.1

  • Active in vitro at concentrations of ≤6 mcg/mL against Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum.1

  • No evidence of doxycycline or multidrug resistance in subgingival plaque or saliva in a clinical study of 6 months’ duration of subgingival doxycycline hyclate.1 6

Advice to Patients

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

  • Doxycycline hyclate polymer for subgingival administration is not meant for self-administration; only qualified oral health-care professionals familiar with administration of the subgingival preparation should administer the drug.1

  • Importance of not using mechanical oral hygiene procedures (i.e., brushing teeth, flossing) for 7 days following administration of the subgingival preparation.1

  • Importance of avoiding exposure to direct sunlight or UV light while receiving oral or subgingival doxycycline hyclate; importance of notifying clinician and of discontinuing therapy at the first sign of skin erythema.1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

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

  • Importance of informing patients of other important precautionary information.1 (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




20 mg (of doxycycline)



Tablets, film-coated

20 mg (of doxycycline)*

Doxycycline Hyclate Tablets



For liquid, extended-release polymer

10% w/w (to deliver 42.5 mg [of doxycycline])

Atridox (available in a 2-syringe Atrigel Delivery System)


AHFS DI Essentials. © Copyright 2018, Selected Revisions June 1, 2006. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


1. CollaGenex Pharmaceuticals. Atridox (doxycycline hyclate 10%) prescribing information. Newtown, PA; 1998 Sep.

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. [PubMed 10695935]

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. [PubMed 10368053]

5. Drisko CH. The use of locally-delivered doxycycline in the treatment of periodontitis. Clinical results. J Clin Periodontol. 1998; 25:947-52. [PubMed 9839851]

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. [PubMed 10872958]

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. [PubMed 11737508]

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. [PubMed 9802705]

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. [PubMed 10522780]

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. [PubMed 10695948]

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. [PubMed 9623893]

12. Garrett S. Local delivery of doxycycline for the treatment of periodontitis. Compendium. 1999; 20:437-46. [PubMed 10650359]

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

14. CollaGenex Pharmaceuticals. Periostat (doxycycline hyclate) 20 mg tablets prescribing information. Newtown, PA; 2003 Oct.

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. [PubMed 10650384]

16. Caton JG. Evaluation of Periostat for patient management. Compend Contin Educ Dent. 1999; 20:451-2,454-6,458-63. [PubMed 10650360]