Get your patient on Doxycycline Hyclate - Doxycycline Hyclate tablet (Doxycycline Hyclate)
Doxycycline Hyclate - Doxycycline Hyclate tablet prescribing information
INDICATIONS AND USAGE
Doxycycline Hyclate is indicated for use as an adjunct to scaling and root planing to promote attachment level gain and to reduce pocket depth in patients with adult periodontitis.
DOSAGE AND ADMINISTRATION
THE DOSAGE OF DOXYCYCLINE HYCLATE DIFFERS FROM THAT OF DOXYCYCLINE USED TO TREAT INFECTIONS. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS INCLUDING THE DEVELOPMENT OF RESISTANT MICROORGANISMS.
Doxycycline hyclate 20 mg twice daily as an adjunct following scaling and root planing may be administered for up to 9 months. Doxycycline hyclate should be taken twice daily at 12 hour intervals, usually in the morning and evening. It is recommended that if doxycycline hyclate is taken close to meal times, allow at least one hour prior to or two hours after meals. Safety beyond 12 months and efficacy beyond 9 months have not been established.
Administration of adequate amounts of fluid along with the tablets is recommended to wash down the drug and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS section).
CONTRAINDICATIONS
This drug is contraindicated in persons who have shown hypersensitivity to doxycycline or any of the other tetracyclines.
ADVERSE REACTIONS
sdverse Reactions in Clinical Trials of a bioequivalent form of doxycycline hyclate capsules: In clinical trials of adult patients with periodontal disease 213 patients received 20 mg BID over a 9 - 12 month period. The most frequent adverse reactions occurring in studies involving treatment with a bioequivalent form of doxycycline hyclate capsules or placebo are listed below:
| Adverse Reaction | Doxycycline Hyclate Capsules 20 mg BID (n=213) | Placebo (n=215) |
|---|---|---|
| Note: Percentages are based on total number of study participants in each treatment group. | ||
| Headache | 55 (26%) | 56 (26%) |
| Common Cold | 47 (22%) | 46 (21%) |
| Flu Symptoms | 24 (11%) | 40 (19%) |
| Tooth Ache | 14 (7%) | 28 (13%) |
| Periodontal Abscess | 8 (4%) | 21 (10%) |
| Tooth Disorder | 13 (6%) | 19 (9%) |
| Nausea | 17 (8%) | 12 (6%) |
| Sinusitis | 7 (3%) | 18 (8%) |
| Injury | 11 (5%) | 18 (8%) |
| Dyspepsia | 13 (6%) | 5 (2%) |
| Sore Throat | 11 (5%) | 13 (6%) |
| Joint Pain | 12 (6%) | 8 (4%) |
| Diarrhea | 12 (6%) | 8 (4%) |
| Sinus Congestion | 11 (5%) | 11 (5%) |
| Coughing | 9 (4%) | 11 (5%) |
| Sinus Headache | 8 (4%) | 8 (4%) |
| Rash | 8 (4%) | 6 (3%) |
| Back Pain | 7 (3%) | 8 (4%) |
| Back Ache | 4 (2%) | 9 (4%) |
| Menstrual Cramp | 9 (4%) | 5 (2%) |
| Acid Indigestion | 8 (4%) | 7 (3%) |
| Pain | 8 (4%) | 5 (2%) |
| Infection | 4 (2%) | 6 (3%) |
| Gum Pain | 1(<1%) | 6 (3%) |
| Bronchitis | 7 (3%) | 5 (2%) |
| Muscle Pain | 2 (1%) | 6 (3%) |
Adverse Reactions for Tetracyclines: The following adverse reactions have been observed in patients receiving tetracyclines:
Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with vaginal candidiasis) in the anogenital region. Hepatotoxicity has been reported rarely. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving the capsule forms of the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. (See DOSAGE AND ADMINISTRATION section).
Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS section).
Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS section).
Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.
Psychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination.
To report SUSPECTED ADVERSE REACTIONS, contact Larken Laboratories, Inc. at 1-601-855-7678 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Drug Interactions
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Since bacterial antibiotics, such as the tetracycline class of antibiotics, may interfere with the bactericidal action of members of the β-lactam (e.g. penicillin) class of antibiotics, it is not advisable to administer these antibiotics concomitantly.
Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron containing preparations, and by bismuth subsalicylate.
Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.
Concurrent use of tetracyclines may render oral contraceptives less effective.
DESCRIPTION
Doxycycline hyclate is available as a 20 mg tablet formulation of doxycycline for oral administration.
The structural formula of doxycycline hyclate is:
with an empirical formula of (C 22 H 24 N 2 O 8 •HCl) 2 •C 2 H 6 O•H 2 O and a molecular weight of 1025.89. The chemical designation for doxycycline is 4-(dimethylamino)-1, 4, 4a, 5, 5a, 6, 11, 12a–octahydro-3, 5, 10, 12, 12a–octahydro-3, 5, 10, 12, 12a-pentahydroxy-6-methyl-1, 11-dioxo-2-naphthacenecarboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate.
Doxycycline hyclate is a yellow to light-yellow crystalline powder which is soluble in water.
CLINICAL PHARMACOLOGY
After oral administration, doxycycline hyclate is rapidly and nearly completely absorbed from the gastrointestinal tract. Doxycycline is eliminated with a half-life of approximately 18 hours by renal and fecal excretion of unchanged drug.
Mechanism of Action:
Doxycycline has been shown to inhibit collagenase activity in vitro . 1 Additional studies have shown that doxycycline reduces the elevated collagenase activity in the gingival crevicular fluid of patients with adult periodontitis. 2,3 The clinical significance of these findings is not known.
Microbiology:
Doxycycline is a member of the tetracycline class of antibiotics. The dosage of doxycycline achieved with this product during administration is well below the concentration required to inhibit microorganisms commonly associated with adult periodontitis. Clinical studies with this product demonstrated no effect on total anaerobic and facultative bacteria in plaque samples from patients administered this dose regimen for 9 to 18 months. This product should not be used for reducing the numbers of or eliminating those microorganisms associated with periodontitis.
Pharmacokinetics
The pharmacokinetics of doxycycline following oral administration of doxycycline hyclate were investigated in 4 volunteer studies involving 107 adults. Additionally, doxycycline pharmacokinetics have been characterized in numerous scientific publications. 4 Pharmacokinetic parameters for doxycycline hyclate following single oral doses and at steady-state in healthy subjects are presented as follows:
| n | C max Mean ± SD (ng/mL) | T max Mean and range (hr) | Cl/F (L/hr) | t1/2 (hr) | |
|---|---|---|---|---|---|
| Single dose 20 mg (tablet) | 20 | 362±101 | 1.4 (1.0-2.5) | 3.85±1.3 | 18.1±4.85 |
| Steady-State 20 mg BID Steady-State data were obtained from normal volunteers administered a bioequivalent formulation. | 30 | 790±285 | 2 (0.98-12.0) | 3.76±1.06 | Not Determined |
Absorption: Doxycycline is well absorbed after oral administration. In a single-dose study, concomitant administration of doxycycline hyclate with a 1000 calorie, high-fat, high-protein meal which included dairy products, in healthy volunteers, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentrations.
Distribution: Doxycycline is greater than 90% bound to plasma proteins. Its apparent volume of distribution is variously reported as between 52.6 and 134 L. 4,6
Metabolism: Major metabolites of doxycycline have not been identified. However, enzyme inducers such as barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.
Excretion: Doxycycline is excreted in the urine and feces as unchanged drug. It is variously reported that between 29% and 55.4% of an administered dose can be accounted for in the urine by 72 hours. 5,6 Half-life averaged 18 hours in subjects receiving a single 20 mg doxycycline dose.
Special Populations
Geriatric: Doxycycline pharmacokinetics have not been evaluated in geriatric patients.
Pediatric: Doxycycline pharmacokinetics have not been evaluated in pediatric patients (See WARNINGS section).
Gender: Doxycycline pharmacokinetics were compared in 9 men and 11 women under fed and fasted conditions. While female subjects had a higher rate (C max ) and extent of absorption (AUC), these differences are thought to be due to differences in body weight/lean body mass. Differences in other pharmacokinetic parameters were not significant.
Race: Differences in doxycycline pharmacokinetics among racial groups have not been evaluated.
Renal Insufficiency: Studies have shown no significant difference in serum half-life of doxycycline in patients with normal and severely impaired renal function. Hemodialysis does not alter the half-life of doxycycline.
Hepatic Insufficiency: Doxycycline pharmacokinetics have not been evaluated in patients with hepatic insufficiency.
Drug Interactions: (See PRECAUTIONS section)
Clinical Study
In a randomized, multi-centered, double-blind, 9-month Phase 3 study involving 190 adult patients with periodontal disease [at least two probing sites per quadrant of between 5 and 9 mm pocket depth (PD) and attachment level (ALv)], the effects of oral administration of 20 mg twice a day of doxycycline hyclate (using a bioequivalent capsule formulation) plus scaling and root planing (SRP) were compared to placebo control plus SRP. Both treatment groups were administered a course of scaling and root planing in 2 quadrants at Baseline. Measurements of ALv, PD and bleeding-on-probing (BOP) were obtained at Baseline, 3, 6, and 9 months from each site about each tooth in the two quadrants that received SRP using the UNC-15 manual probe. Each tooth site was categorized into one of three strata based on Baseline PD: 0-3 mm (no disease), 4-6 mm (mild/moderate disease), ≥ 7 mm (severe disease). For each stratum and treatment group, the following were calculated at month 3, 6, and 9: mean change in ALv from baseline, mean change in PD from baseline, mean percentage of tooth sites per patient exhibiting attachment loss of ≥ 2 mm from baseline, and percentage of tooth sites with bleeding on probing. The results are summarized in the following table.
| Parameter | Baseline Pocket Depth | ||
|---|---|---|---|
| 0-3 mm | 4-6 mm | ≥ 7 mm | |
| Number of Patients (Doxycycline Hyclate 20mg BID) | 90 | 90 | 79 |
| Number of Patients (Placebo) | 93 | 93 | 78 |
| Mean Gain (SD) in ALv Alv=Clinical Attachment Level | |||
| Doxycycline hyclate 20 mg BID | 0.25 (0.29) mm | 1.03 (0.47) mm p<0.050 vs. the placebo control group. | 1.55 (1.16)mm |
| Placebo | 0.20 (0.29) mm | 0.86 (0.48) mm | 1.17 (1.15) mm |
| Mean Decrease (SD SD=Standard Deviation ) in PD PD=Pocket Depth | |||
| Doxycycline hyclate 20 mg BID | 0.16 (0.19) mm p<0.010 vs. the placebo control group. | 0.95 (0.47) mm | 1.68 (1.07)mm |
| Placebo | 0.05 (0.19) mm | 0.69 (0.48) mm | 1.20 (1.06) mm |
| % of Sites (SD) with loss of ALv≥ 2 mm | |||
| Doxycycline hyclate 20 mg BID | 1.9 (4.2)% | 1.3 (4.5)% | 0.3 (9.4)% |
| Placebo | 2.2 (4.1)% | 2.4 (4.4)% | 3.6 (9.4)% |
| % of Sites (SD) with BOP BOP=Bleeding on Probing | |||
| Doxycycline hyclate 20 mg BID | 39 (19)% | 64 (18)% | 75 (29)% |
| Placebo | 46 (19)% | 70 (18)% | 80 (29)% |
Clinical Study
In a randomized, multi-centered, double-blind, 9-month Phase 3 study involving 190 adult patients with periodontal disease [at least two probing sites per quadrant of between 5 and 9 mm pocket depth (PD) and attachment level (ALv)], the effects of oral administration of 20 mg twice a day of doxycycline hyclate (using a bioequivalent capsule formulation) plus scaling and root planing (SRP) were compared to placebo control plus SRP. Both treatment groups were administered a course of scaling and root planing in 2 quadrants at Baseline. Measurements of ALv, PD and bleeding-on-probing (BOP) were obtained at Baseline, 3, 6, and 9 months from each site about each tooth in the two quadrants that received SRP using the UNC-15 manual probe. Each tooth site was categorized into one of three strata based on Baseline PD: 0-3 mm (no disease), 4-6 mm (mild/moderate disease), ≥ 7 mm (severe disease). For each stratum and treatment group, the following were calculated at month 3, 6, and 9: mean change in ALv from baseline, mean change in PD from baseline, mean percentage of tooth sites per patient exhibiting attachment loss of ≥ 2 mm from baseline, and percentage of tooth sites with bleeding on probing. The results are summarized in the following table.
| Parameter | Baseline Pocket Depth | ||
|---|---|---|---|
| 0-3 mm | 4-6 mm | ≥ 7 mm | |
| Number of Patients (Doxycycline Hyclate 20mg BID) | 90 | 90 | 79 |
| Number of Patients (Placebo) | 93 | 93 | 78 |
| Mean Gain (SD) in ALv Alv=Clinical Attachment Level | |||
| Doxycycline hyclate 20 mg BID | 0.25 (0.29) mm | 1.03 (0.47) mm p<0.050 vs. the placebo control group. | 1.55 (1.16)mm |
| Placebo | 0.20 (0.29) mm | 0.86 (0.48) mm | 1.17 (1.15) mm |
| Mean Decrease (SD SD=Standard Deviation ) in PD PD=Pocket Depth | |||
| Doxycycline hyclate 20 mg BID | 0.16 (0.19) mm p<0.010 vs. the placebo control group. | 0.95 (0.47) mm | 1.68 (1.07)mm |
| Placebo | 0.05 (0.19) mm | 0.69 (0.48) mm | 1.20 (1.06) mm |
| % of Sites (SD) with loss of ALv≥ 2 mm | |||
| Doxycycline hyclate 20 mg BID | 1.9 (4.2)% | 1.3 (4.5)% | 0.3 (9.4)% |
| Placebo | 2.2 (4.1)% | 2.4 (4.4)% | 3.6 (9.4)% |
| % of Sites (SD) with BOP BOP=Bleeding on Probing | |||
| Doxycycline hyclate 20 mg BID | 39 (19)% | 64 (18)% | 75 (29)% |
| Placebo | 46 (19)% | 70 (18)% | 80 (29)% |
HOW SUPPLIED
Doxycycline hyclate are white film coated, round, biconvex tablet, debossed LL714 on one side and plain on the other side containing doxycycline hyclate equivalent to 20 mg doxycycline. Bottle of 60 tablets (NDC 68047-714-60) and Bottle of 100 tablets (NDC 68047-714-01).
Storage and Handling
Store at 20°-25°C (68°-77°F). [See USP Controlled Room Temperature].
Dispense in tight, light-resistant containers (USP).
Manufactured for:
Larken Laboratories, Inc .
Canton, MS 39046
www.larkenlabs.com
201095-01
Rev. 07/25
Mechanism of Action:
Doxycycline has been shown to inhibit collagenase activity in vitro . 1 Additional studies have shown that doxycycline reduces the elevated collagenase activity in the gingival crevicular fluid of patients with adult periodontitis. 2,3 The clinical significance of these findings is not known.
