Professional Information
Doxycycline (Systemic)
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VA CLASSIFICATION
Primary: XX000
Commonly used brand name(s): Periostat.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Enzyme inhibitor (dental)—
Indications
General considerations
The dose of doxycycline used for adult periodontitis produces systemic concentrations well below those required to inhibit associated microorganisms. In patients who received the medication for 9 to 18 months, this doxycycline formulation was not found to have any effect on total anaerobic and facultative bacteria in plaque samples. {01}{02}
Accepted
Periodontitis (treatment adjunct)—Doxycycline hyclate tablets are indicated as an adjunct therapy to scaling and root planing to promote attachment level gain and to reduce pocket depth in adults with periodontitis {01}{02}.
Note: This doxycycline formulation is not indicated for reduction or elimination of microorganisms associated with periodontitis {01}{02}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
Doxycycline hyclate: 1025.89 {01}{02}
Solubility
Soluble in water {01}{02}.
Mechanism of action/Effect:
Although the exact mechanism of action is not known, doxycycline inhibits collagenase activity in vitro and has been found to decrease the increased collagenase activity in the gingival crevicular fluid of patients with adult periodontitis {01}{02}.
Other actions/effects:
Although doxycycline is a tetracycline antibiotic, systemic concentrations achieved with this formulation are too low to produce any antibacterial activity {01}{02}.
Absorption:
Rapid and nearly complete {01}{02}.
Distribution:
Apparent volume of distribution is between 52.6 and 134 L {01}{02}.
Protein binding:
Plasma—Very high (> 90%) {01}{02}.
Half-life:
After a single dose—Approximately 18 hours {01}{02}.
Time to peak plasma concentration
Single dose—1.4 hours (range 1 to 2.5 hours){02}.
Steady-state—2 hours (range 0.98 to 12 hours) {01}{02}.
Peak plasma concentration
Single 20-mg dose—362 (± 101) nanograms per mL{02}.
Steady-state at dose of 20 mg twice a day—790 (± 285) nanograms per mL {01}{02}.
Elimination:
Renal/fecal, as unchanged drug {01}{02}.
In dialysis—
Hemodialysis does not alter the half-life of doxycycline {01}{02}.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to one tetracycline may also be sensitive to other tetracyclines {01}.
Carcinogenicity
Long-term studies with doxycycline in animals have not been done. However, there was evidence of oncogenicity in studies with related compounds, including adrenal and pituitary tumors with oxytetracycline and thyroid tumors with minocycline. {01}
Mutagenicity
Doxycycline was not found to be mutagenic in an in vitro point mutation study with mammalian cells (CHO/HGPRT forward mutation assay) or in an in vivo micronucleus assay in CD-1 mice. However, in an in vitro study with CHO cells for the potential to cause chromosomal aberrations, the data suggested that doxycycline is a weak clastogen. {01}
Pregnancy/Reproduction
Fertility—
Adverse effects on fertility and reproductive performance were observed in both male and female Sprague-Dawley rats given oral doxycyline hyclate. {01} These effects included increased time required for mating to occur, reduced sperm motility, velocity, and concentration, abnormal sperm morphology, and increased preimplantation and postimplantation losses. {01} A range of doses of doxycycline hyclate was studied; the lowest dose tested was 50 milligrams per kilogram of body weight per day (mg/kg/day). {01} All doses studied resulted in reproductive toxicity, including the lowest dose, which resulted in a significant reduction in sperm velocity. {01} The 50 mg/kg/day dose is approximately ten times the recommended daily dose of doxycycline, when used as an enzyme inhibitor, for a 60-kg human. {01} The effect of doxycycline hyclate on human fertility is not known. {01}
Pregnancy—
Administration of doxycycline to pregnant women can harm the fetus {01}.
In animals, doxycycline crosses the placenta and appears in fetal tissues. Tetracyclines have been found to cause fetotoxicity, often related to retardation of skeletal development. Also, tetracyclines administered early in pregnancy have been found to cause embryotoxicity. {01}
Use of tetracyclines is not recommended during the last half of pregnancy since they may cause permanent discoloration of teeth, enamel hypoplasia, and inhibition of skeletal growth. Before use during pregnancy, or if pregnancy occurs during treatment with doxycycline, the patient should be informed of the potential risks. {01}
FDA Pregnancy Category D {01}.
Breast-feeding
Tetracyclines are distributed into human breast milk. Use of doxycycline is not recommended in nursing mothers because of the risk of permanent discoloration of teeth and enamel hypoplasia in the infant. {01}
Pediatrics
In infants and children up to 8 years of age, tetracyclines may cause permanent discoloration (yellow-gray-brown) of teeth and enamel hypoplasia. Therefore, use is not recommended in patients in these age groups. {01}
Because tetracyclines form a stable calcium complex in any bone-forming tissue, a decrease in fibular growth rate may occur. However, this effect is reversible when the medication is withdrawn. {01}
Geriatrics
No information is available on the relationship of age to the effects of doxycycline in geriatric patients {01}.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
» Antacids, aluminum-, calcium-, or magnesium-containing {01} or
» Bismuth subsalicylate {01} or
» Iron supplements {01} (absorption of tetracyclines may be decreased {01})
» Anticoagulants {01} (tetracyclines may depress plasma prothrombin activity; anticoagulant dosage may need to be decreased {01})
Barbiturates {01} or
Carbamazepine {01} or
Phenytoin {01} (concurrent use may decrease the half-life of doxycycline)
» Contraceptives, oral (concurrent use with tetracyclines may result in decreased effectiveness of oral contraceptives {01})
» Methoxyflurane {01} (concurrent use with tetracyclines has been reported to lead to fatal nephrotoxicity {01})
» Penicillins {01} (since bacteriostatic drugs may interfere with the bactericidal effect of beta-lactam antibiotics [especially penicillins], it is best to avoid concurrent therapy {01})
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With diagnostic test results
Catecholamine determinations, urine (may produce false elevations of urinary catecholamines because of interference with fluorescence in the Hingerty method {01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Candidiasis, oral, history of or predisposition to {01} (caution is recommended; safety and efficacy in treatment of periodontitis in patients with coexisting oral candidiasis have not been established {01})
» Hypersensitivity to doxycycline or other tetracyclines {02}
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Hematopoietic, hepatic, and renal system function{02} (periodic monitoring recommended during long-term treatment{02})
Side/Adverse Effects
Note: Although not reported during clinical studies, overgrowth of nonsusceptible organisms (including fungi and yeasts) could theoretically occur {01}. Treatment with tetracyclines may increase the risk of vaginal candidiasis {01}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence rare
Fungal overgrowth{01} (itching of the rectal or genital areas; sore mouth or tongue)
photosensitivity {01}(increased sensitivity of skin to sunlight)
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
Diarrhea{01}
dyspepsia{01} (heartburn{01})
joint pain
nausea
Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Treatment of overdose
Withdrawal of doxycycline, along with symptomatic and supportive measures, is recommended {01}.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Doxycycline—For Dental Use (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Hypersensitivity to doxycycline or other tetracyclines
Pregnancy—Tetracyclines cross the placenta; use is not recommended during the last half of pregnancy since tetracyclines may cause permanent discoloration of teeth, enamel hypoplasia, and inhibition of skeletal growth in the fetus
Breast-feeding—Tetracyclines are distributed into human breast milk; use is not recommended, because of the risk of permanent discoloration of teeth and enamel hypoplasia in the breast-fed infant
Use in children—Use is not recommended in infants and children up to 8 years of age because tetracyclines may cause permanent discoloration of teeth and enamel hypoplasia
Other medications, especially antacids, anticoagulants, bismuth subsalicylate, iron supplements, methoxyflurane, oral contraceptives, or penicillins
Proper use of this medication
Taking one hour before the morning and evening meals
Taking with at least a full glass of water while in an upright position, to avoid esophageal ulceration and to decrease gastrointestinal irritation
» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses
» Proper storage
Precautions while using this medication
» Avoiding antacids, bismuth subsalicylate, and iron supplements within 1 to 3 hours of a doxycycline hyclate dose
» Using an alternate or additional method of contraception if concurrently taking estrogen-containing oral contraceptives
» Caution if surgery with general anesthesia is required because of risk of nephrotoxicity with concurrent use of methoxyflurane
» Possible photosensitivity reactions
Side/adverse effects
Signs of potential side effects, especially fungal overgrowth or photosensitivity
General Dosing Information
It is recommended that doxycycline be taken with adequate amounts of fluid to help wash down the medication and reduce the risk of esophageal irritation and ulceration {01}.
It is recommended that the usual adult dose not be exceeded, because of the risk of increased side/adverse effects and development of resistant microorganisms {01}.
It is recommended that doxycycline treatment be withdrawn at the first sign of skin erythema, which may be a symptom of photosensitivity {01}.
Diet/Nutrition
It is recommended that doxycycline be taken at least 1 hour before morning and evening meals {01}.
Oral Dosage Forms
DOXYCYCLINE HYCLATE TABLETS USP
Note: Strength and dose of doxycycline hyclate tablets are expressed in terms of the base {02}.
Usual adult dose
Periodontitis (treatment adjunct)
Oral, 20 mg (base) twice a day {02}.
Note: Doxycycline hyclate is given as an adjunct following scaling and root planing and may be administered for up to nine months. Safety and efficacy beyond twelve months and nine months, respectively, have not been established. {02}
The recommended adult dose is different from the dose used to treat infections. Use of doses higher than the recommended dose may lead to increased side/adverse effects and the development of resistant microorganisms. {02}
Usual pediatric dose
Periodontitis (treatment adjunct)
Children up to 8 years of age: Use is not recommended {02}.
Children 8 years of age and older: Safety and efficacy have not been established.{02}
Strength(s) usually available
U.S.—
20 mg (base) (Rx) [Periostat (lactose)]{02}
Packaging and storage:
Store between 15 and 30 ºC (59 and 86 ºF), unless otherwise specified by manufacturer {02}. Protect from light {02}.
Developed: 01/14/1999
Revised: 07/31/2001
References
- Periostat package insert (Collagenex—US), Rec 10/13/98.
- Product information: Periostat®, doxycycline hyclate tablets. CollaGenex Pharmaceuticals, Newtown, PA, (PI revised 4/2001) reviewed 7/2001.
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