Antiinfectives and antiseptics for local oral treatment

Doxycycline Hyclate

Approved 30 Jun 2020OralTablet

The FDA lists this product in 60 strengths and forms.

Indications

Doxycycline hyclate tablets are tetracycline class drugs indicated for: · Rickettsial infections (1.1) · Sexually transmitted infections (1.2) · Respiratory tract infections (1.3) · Specific bacterial infections (1.4) · Ophthalmic infections (1.5) · Anthrax, including inhalational anthrax (post-exposure) (1.6) · Alternative treatment for selected infections when penicillin is contraindicated (1.7) · Adjunctive therapy for acute intestinal amebiasis and severe acne (1.8) · Prophylaxis of malaria (1.9) To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate tablets and other antibacterial drugs, doxycycline hyclate tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

(1.10)

1.1Rickettsial Infections

Doxycycline hyclate tablets are indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, and tick fevers caused by Rickettsiae .

1.2Sexually Transmitted Infections

Doxycycline hyclate tablets are indicated for treatment of the following sexually transmitted infections: Uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis . Nongonococcal urethritis caused by Ureaplasma urealyticum . Lymphogranuloma venereum caused by Chlamydia trachomatis . Granuloma inguinale caused by Klebsiella granulomatis . Uncomplicated gonorrhea caused by Neisseria gonorrhoeae .

Chancroid caused by Haemophilus ducreyi .

1.3Respiratory Tract Infections

Doxycycline hyclate tablets are indicated for treatment of the following respiratory tract infections: Respiratory tract infections caused by Mycoplasma pneumoniae . Psittacosis (ornithosis) caused by Chlamydophila psittaci . Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended. Doxycycline is indicated for treatment of infections caused by the following microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug: Respiratory tract infections caused by Haemophilus influenzae .

Warnings and precautions

The use of doxycycline hyclate tablets during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. Advise the patient of the potential risk to the fetus during pregnancy. (2.2, 5.1, 8.1, 8.4) The use of doxycycline hyclate tablets during the second and third-trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth.

Advise the patient of the potential risk to the fetus during pregnancy. (5.2, 8.1, 8.4) Clostridioides difficile -associated diarrhea (CDAD) has been reported. Evaluate patients if diarrhea occurs. (5.3) Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Limit sun exposure. (5.4) Overgrowth of non-susceptible organisms, including fungi, may occur.

If such infections occur, discontinue use and institute appropriate therapy. (5.10)

5.1Tooth Development

The use of doxycycline hyclate tablets during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drugs of the tetracycline-class, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with drugs of the tetracycline class.

Advise the patient of the potential risk to the fetus if doxycycline hyclate tablet is used during pregnancy [see Use in Specific Populations (8.1, 8.4)] . Use doxycycline hyclate tablets in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.

5.2Inhibition of Bone Growth

The use of doxycycline hyclate tablets during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.

Advise the patient of the potential risk to the fetus if doxycycline hyclate tablet is used during pregnancy [see Use in Specific Populations (8.1, 8.4)] .

5.3 Clostridioides difficile Associated Diarrhea Clostridioides difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline hyclate tablets, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD.

Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued.

Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.

5.4Photosensitivity

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

5.5Severe Skin Reactions

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline [See Adverse Reactions (6)] . If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.

5.6Intracranial Hypertension

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline hyclate tablets. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and doxycycline hyclate tablets should be avoided because isotretinoin is also known to cause pseudotumor cerebri.

Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.

5.7Antianabolic Action

The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

5.8Incomplete Suppression of Malaria

Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains. Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.

5.9Development of Drug-Resistant Bacteria

Prescribing doxycycline hyclate tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

5.10Potential for Microbial Overgrowth

Doxycycline hyclate tablets may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue use and institute appropriate therapy.

5.11Laboratory Monitoring for Long-Term Therapy

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Doxycycline hyclate tablets, like other tetracycline-class antibacterial drugs, may cause discoloration deciduous teeth, and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy [see Warnings and Precautions (5.1) and (5.2)]. Available data from published studies over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure in the first trimester of pregnancy ( see Data ).

There are no available data on the risk of miscarriage following exposure to doxycycline in pregnancy. Advise the patient of the potential risk to the fetus if doxycycline hyclate tablet is used during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Human Data A retrospective cohort study of 1,690 pregnant patients who received doxycycline prescriptions in the first trimester of pregnancy compared to an unexposed pregnant cohort showed no difference in the major malformation rate. There is no information on the dose or duration of treatment, or if the patients actually ingested the doxycycline that was prescribed. Other published studies on exposure to doxycycline in the first trimester of pregnancy have small sample sizes; however, these studies have not shown an increased risk of major malformations.

The use of tetracyclines during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses [see Warnings and Precautions (5.1, 5.2)]. Animal Data Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development).

Evidence of embryotoxicity also has been noted in animals treated early in pregnancy.

Adverse reactions

The following adverse reactions have been identified during clinical trials or post-approval use of tetracycline-class drugs, including doxycycline. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis.

Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development [See Warnings and Precautions (5.1)] .

Instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline-class. Most of these patients took medications immediately before going to bed [see Dosage and Administration (2.1)]. Skin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, and erythema multiforme have been reported.

Photosensitivity has been reported [see Warnings and Precautions (5.4)]. Renal: Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions (5.7)]. Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus, and drug reaction with eosinophilia and systemic symptoms (DRESS). Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.

Intracranial Hypertension: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines [see Warnings and Precautions (5.6)]. Thyroid Gland Changes: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur. Adverse reactions observed in patients receiving tetracyclines include anorexia, nausea, vomiting, diarrhea, rash, photosensitivity, urticaria, and hemolytic anemia.

(6) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Indications

1.1Rickettsial Infections

1.2Sexually Transmitted Infections

1.3Respiratory Tract Infections

Two medicines in one question?

1.4Specific Bacterial Infections

1.5Ophthalmic Infections

1.6Anthrax Including Inhalational Anthrax (Post-Exposure)

1.7Alternative Treatment for Selected

1.8Adjunctive Therapy for Acute Intestinal Amebiasis and Severe Acne

1.9Prophylaxis of Malaria

1.10Usage

Contraindications

Warnings and precautions

5.1Tooth Development

5.2Inhibition of Bone Growth

5.4Photosensitivity

5.5Severe Skin Reactions

5.6Intracranial Hypertension

5.7Antianabolic Action

5.8Incomplete Suppression of Malaria

5.9Development of Drug-Resistant Bacteria

5.10Potential for Microbial Overgrowth

5.11Laboratory Monitoring for Long-Term Therapy

Interactions

7.1Anticoagulant Drugs

7.2Penicillin

7.3Antacids and Iron Preparations Absorption

7.4Oral Contraceptives

7.5Barbiturates and Anti-Epileptics

7.6Penthrane®

7.7Drug and Laboratory Test Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance

Guidelines