Doxycycline Hyclate

Doxycycline hyclate delayed-release tablets are a tetracycline-class drug indicated for:

• Rickettsial infections (
  1.1 Rickettsial Infections

  Doxycycline hyclate delayed-release tablets are indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by

  Rickettsiae

  .
  )
• Sexually transmitted infections (
  1.2 Sexually Transmitted Infections

  Doxycycline hyclate delayed-release 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
    .
  )
• Respiratory tract infections (
  1.3 Respiratory Tract Infections

  Doxycycline hyclate delayed-release tablets are indicated for treatment of the following respiratory 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 micro- organisms, when bacteriological testing indicates appropriate susceptibility to the drug:
    • –Respiratory tract infections caused by
      Haemophilus influenzae
      .
    • –Respiratory tract infections caused by
      Klebsiella
      species.
    • –Upper respiratory infections caused by
      Streptococcus pneumoniae
      .
  )
• Specific bacterial infections (
  1.4 Specific Bacterial Infections

  Doxycycline hyclate delayed-release tablets are indicated for treatment of the following specific bacterial infections:

  • Relapsing fever due to
    Borrelia recurrentis
    .
  • Plague due to
    Yersinia pestis
    .
  • Tularemia due to
    Francisella tularensis
    .
  • Cholera caused by
    Vibrio cholerae
    .
  • Campylobacter fetus infections caused by
    Campylobacter fetus
    .
  • Brucellosis due to
    Brucella
    species (in conjunction with streptomycin).
  • Bartonellosis due to
    Bartonella bacilliformis
    .

  Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.

  Doxycycline hyclate delayed-release tablets are indicated for treatment of infections caused by the following gram- negative microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug:

  • Escherichia coli
  • Enterobacter aerogenes
  • Shigella
    species
  • Acinetobacter
    species
  • Urinary tract infections caused by
    Klebsiella
    species.
  )
• Ophthalmic infections (
  1.5 Ophthalmic Infections

  Doxycycline hyclate delayed-release tablets are indicated for treatment of the following ophthalmic infections:

  • Trachoma caused by
    Chlamydia trachomatis
    , although the infectious agent is not always eliminated as judged by immunofluorescence.
  • Inclusion conjunctivitis caused by
    Chlamydia trachomatis
    .
  )
• Anthrax, including inhalational anthrax (post-exposure) (
  1.6 Anthrax Including Inhalational Anthrax (Post-Exposure)

  Doxycycline hyclate delayed-release tablets are indicated for the treatment of anthrax due to

  Bacillus anthracis

  , including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized

  Bacillus anthracis

  .
  )
• Alternative treatment for selected infections when penicillin is contraindicated (
  1.7 Alternative Treatment for Selected Infections When Penicillin is Contraindicated

  Doxycycline hyclate delayed-release tablets are indicated as an alternative treatment for the following selected infections when penicillin is contraindicated:

  • Syphilis caused by
    Treponema pallidum
    .
  • Yaws caused by
    Treponema pallidum
    subspecies
    pertenue
    .
  • Vincent's infection caused by
    Fusobacterium fusiforme.
  • Actinomycosis caused by
    Actinomyces israelii
    .
  • Infections caused by
    Clostridium
    species.
  )
• Adjunctive therapy in acute intestinal amebiasis and severe acne (
  1.8 Adjunctive Therapy for Acute Intestinal Amebiasis and Severe Acne

  In acute intestinal amebiasis, doxycycline hyclate delayed-release tablets may be a useful adjunct to amebicides.

  In severe acne, doxycycline may be useful adjunctive therapy.
  )
• Prophylaxis of malaria (
  1.9 Prophylaxis of Malaria

  Doxycycline hyclate delayed-release tablets are indicated for the prophylaxis of malaria due to

  Plasmodium falciparum

  in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains [

  see Dosage and Administration (2.2)and Patient Counseling Information (17)

  ].
  )

To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate delayed-release tablets and other antibacterial drugs, Doxycycline hyclate delayed-release tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (

• Dosage in Adult Patients:
  • The usual dosage is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg daily. (
    2.1 Important Dosage and Administration Instructions

    • Doxycycline hyclate delayed-release tablets are not substitutable on a mg per mg basis with other oral doxycyclines. To avoid prescribing errors, do not substitute doxycycline hyclate delayed-release tablets for other oral doxycyclines on a mg per mg basis because of differing bioavailability.
    • Do not chew or crush tablets
      [see Dosage and Administration (2.4)]
      .
    • The recommended dosage, frequency of administration and weight-based dosage recommendations of doxycycline hyclate delayed-release tablets differ from that of the other tetracyclines
      [see Dosage and Administration (2.2, 2.3, 2.4)]
      . Exceeding the recommended dosage may result in
      
      an increased incidence of adverse reactions.
    • Administer doxycycline hyclate delayed-release tablets with an adequate amount of fluid to wash down the drug and reduce the risk of esophageal irritation and ulceration
      [see Adverse Reactions (6.1)]
      .
    • If gastric irritation occurs, doxycycline hyclate delayed-release tablets may be given with food or milk
      [see Clinical Pharmacology (12.3)]
      .
    )
  • In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended. (
    2.1 Important Dosage and Administration Instructions

    • Doxycycline hyclate delayed-release tablets are not substitutable on a mg per mg basis with other oral doxycyclines. To avoid prescribing errors, do not substitute doxycycline hyclate delayed-release tablets for other oral doxycyclines on a mg per mg basis because of differing bioavailability.
    • Do not chew or crush tablets
      [see Dosage and Administration (2.4)]
      .
    • The recommended dosage, frequency of administration and weight-based dosage recommendations of doxycycline hyclate delayed-release tablets differ from that of the other tetracyclines
      [see Dosage and Administration (2.2, 2.3, 2.4)]
      . Exceeding the recommended dosage may result in
      
      an increased incidence of adverse reactions.
    • Administer doxycycline hyclate delayed-release tablets with an adequate amount of fluid to wash down the drug and reduce the risk of esophageal irritation and ulceration
      [see Adverse Reactions (6.1)]
      .
    • If gastric irritation occurs, doxycycline hyclate delayed-release tablets may be given with food or milk
      [see Clinical Pharmacology (12.3)]
      .
    )
• Dosage in Pediatric Patients:
  • For all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever), the recommended dose is 2.2 mg per kg of body weight administered every 12 hours. Pediatric patients weighing 45 kg or more should receive the adult dose. (
    2.1 Important Dosage and Administration Instructions

    • Doxycycline hyclate delayed-release tablets are not substitutable on a mg per mg basis with other oral doxycyclines. To avoid prescribing errors, do not substitute doxycycline hyclate delayed-release tablets for other oral doxycyclines on a mg per mg basis because of differing bioavailability.
    • Do not chew or crush tablets
      [see Dosage and Administration (2.4)]
      .
    • The recommended dosage, frequency of administration and weight-based dosage recommendations of doxycycline hyclate delayed-release tablets differ from that of the other tetracyclines
      [see Dosage and Administration (2.2, 2.3, 2.4)]
      . Exceeding the recommended dosage may result in
      
      an increased incidence of adverse reactions.
    • Administer doxycycline hyclate delayed-release tablets with an adequate amount of fluid to wash down the drug and reduce the risk of esophageal irritation and ulceration
      [see Adverse Reactions (6.1)]
      .
    • If gastric irritation occurs, doxycycline hyclate delayed-release tablets may be given with food or milk
      [see Clinical Pharmacology (12.3)]
      .
    )
  • For pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45 kg), the recommended dose is 4.4 mg per kg of body weight divided into two doses on the first day of treatment, followed by a maintenance dose of 2.2 mg per kg of body weight (given as a single daily dose or divided into two doses). For pediatric patients weighing over 45 kg, the usual adult dose should be used. (
    2.1 Important Dosage and Administration Instructions

    • Doxycycline hyclate delayed-release tablets are not substitutable on a mg per mg basis with other oral doxycyclines. To avoid prescribing errors, do not substitute doxycycline hyclate delayed-release tablets for other oral doxycyclines on a mg per mg basis because of differing bioavailability.
    • Do not chew or crush tablets
      [see Dosage and Administration (2.4)]
      .
    • The recommended dosage, frequency of administration and weight-based dosage recommendations of doxycycline hyclate delayed-release tablets differ from that of the other tetracyclines
      [see Dosage and Administration (2.2, 2.3, 2.4)]
      . Exceeding the recommended dosage may result in
      
      an increased incidence of adverse reactions.
    • Administer doxycycline hyclate delayed-release tablets with an adequate amount of fluid to wash down the drug and reduce the risk of esophageal irritation and ulceration
      [see Adverse Reactions (6.1)]
      .
    • If gastric irritation occurs, doxycycline hyclate delayed-release tablets may be given with food or milk
      [see Clinical Pharmacology (12.3)]
      .
    )

Doxycycline hyclate delayed-release tablets, USP 80 mg are white, oval scored tablets containing yellow pellets and debossed with "D|8" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 80 mg of doxycycline.

Doxycycline hyclate delayed-release tablets, 200 mg are white, oval scored tablets containing yellow pellets and debossed with "D|D" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 200 mg of doxycycline.

• Tetracycline-class drugs can cause fetal harm when administered to a pregnant woman, but data for doxycycline are limited. (
  5.6 Intracranial Hypertension

  Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracycline including doxycycline hyclate delayed-release 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. Avoid concomitant use of isotretinoin and doxycycline hyclate delayed-release tablets 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.
  ,
  8.1 Pregnancy

  Risk Summary

  There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for the treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk

  (see Data)

  .¹

  In the US general population the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

  Clinical Considerations

  Embryo/Fetal Risk

  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. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus

  [see Warnings and Precautions (5.1, 5.6)].

  Data

  Human Data

  A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and 56 (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (that is, in the second and third months of gestation), with the exception of a marginal relationship with neural tube defect based on only two-exposed cases.²

  A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.³
  )
• Tetracyclines are excreted in human milk; however, the extent of absorption of doxycycline in the breastfed infant is not known. Doxycycline hyclate delayed-release tablets use during nursing should be avoided if possible. (
  8.2 Lactation

  Risk Summary

  Tetracyclines are excreted in human milk, however, the extent of absorption of tetracyclines including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated. The effects of prolonged exposure to doxycycline in breast milk production and breast fed neonates, infants and children are unknown⁴. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for doxycycline hyclate delayed-release tablets and any potential adverse effects on the breast fed child from doxycycline hyclate delayed-release tablets or from the underlying maternal condition [

  see Warnings and Precautions (5.1, 5.6)

  ].
  )