Acticlate

Doxycycline is a tetracycline antibiotic. It fights bacteria in the body.

Doxycycline is used to treat many different bacterial infections, such as acne, urinary tract infections, intestinal infections, eye infections, gonorrhea, chlamydia, periodontitis (gum disease), and others.

Doxycycline is also used to treat blemishes, bumps, and acne-like lesions caused by rosacea. Doxycycline will not treat facial redness caused by rosacea.

Some forms of doxycycline are used to prevent malaria, to treat anthrax, or to treat infections caused by mites, ticks, or lice.

Doxycycline may also be used for purposes not listed in this medication guide.

You should not take this medicine if you are allergic to any tetracycline antibiotic.

Children should not use doxycycline. Doxycycline can cause permanent yellowing or graying of the teeth in children younger than 8 years old.

You should not take this medicine if you are allergic to doxycycline or other tetracycline antibiotics such as demeclocycline, minocycline, tetracycline, or tigecycline.

To make sure doxycycline is safe for you, tell your doctor if you have:

• liver disease;
• kidney disease;
• asthma or sulfite allergy;
• a history of increased pressure inside your skull;
• if you also take isotretinoin (Amnesteem, Claravis, Sotret); or
• if you take seizure medicine (carbamazepine, phenobarbital, phenytoin), or a blood thinner (warfarin, Coumadin, Jantoven).

If you are using doxycycline to treat gonorrhea, your doctor may test you to make sure you do not also have syphilis, another sexually transmitted disease.

Do not use doxycycline if you are pregnant. It could harm the unborn baby or cause permanent tooth discoloration later in life. Tell your doctor right away if you become pregnant during treatment.

Doxycycline can make birth control pills less effective. Ask your doctor about using a non hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while using doxycycline.

Doxycycline passes into breast milk and may affect bone and tooth development in a nursing baby. You should not breast-feed while you are taking doxycycline.

Children should not use doxycycline. Doxycycline can cause permanent yellowing or graying of the teeth in children younger than 8 years old.

You should not take this medicine if you are allergic to any tetracycline antibiotic.

Children younger than 8 years old should use doxycycline only in cases of severe or life-threatening conditions. This medicine can cause permanent yellowing or graying of the teeth in children

Using doxycycline during pregnancy could harm the unborn baby or cause permanent tooth discoloration later in the baby's life.

Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours before or after taking doxycycline.

Avoid taking any other antibiotics with doxycycline unless your doctor has told you to.

Avoid exposure to sunlight or tanning beds. Doxycycline can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

• If you have an allergy to doxycycline or any other part of Acticlate (doxycycline tablets and capsules).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are taking any of these drugs: Acitretin, isotretinoin, or a penicillin.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Acticlate with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have your blood work checked if you are on Acticlate for a long time. Talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• Do not use longer than you have been told. A second infection may happen.
• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• Do not switch between different forms of Acticlate without first talking with the doctor.
• If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
• A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
• Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy. Use some other kind of birth control also like a condom when taking Acticlate.
• This medicine may cause a change in tooth color to yellow-gray-brown in children younger than 8 years old. If this change of tooth color happens, it will not go away. Talk with the doctor.
• Most of the time, this medicine is not for use in children younger than 8 years old. However, there may be times when these children may need to take Acticlate. Talk with the doctor.
• Change in tooth color has also happened in adults. This has gone back to normal after this medicine was stopped and teeth cleaning at a dentist's office. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Acticlate, call your doctor right away.

Acticlate and Acticlate CAP are contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

Mechanism of Action

Doxycycline is a tetracycline-class antimicrobial drug [see Microbiology (12.4)].

Pharmacokinetics

Absorption
Acticlate (doxycycline hyclate) Tablets: Following administration of a single 300 mg dose to adult volunteers, average peak plasma doxycycline levels were 3.0 mcg per mL at 3 hours, decreasing to 1.18 mcg per mL at 24 hours. The mean Cmax and AUC0-∞ of doxycycline are 24% and 15% lower, respectively, following single dose administration of Acticlate, 150 mg tablets with a high fat meal (including milk) compared to fasted conditions. The clinical significance of these decreases is unknown.
Acticlate CAP (doxycycline hyclate) Capsules. Following administration of a single 300 mg dose to adult volunteers, average peak plasma doxycycline levels were 2.8 mcg per mL at 3 hours, decreasing to 1.1 mcg per mL at 24 hours. The mean Cmax of doxycycline is approximately 20% lower and the AUC0-∞ is unchanged following single dose administration of Acticlate CAP Capsules with a high fat meal (including milk) compared to fasted conditions. The clinical significance of this decrease in Cmax is unknown.

Excretion
Tetracyclines are concentrated in bile by the liver and excreted in the urine and feces at high concentrations and in a biologically active form.

Excretion of doxycycline by the kidney is about 40% per 72 hours in individuals with a creatinine clearance of about 75 mL per minute. This percentage may fall as low as 1% per 72 hours to 5% per 72 hours in individuals with a creatinine clearance below 10 mL per minute. Studies have shown no significant difference in the serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter the serum half-life.

Microbiology

Mechanism of Action
Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.
Resistance
Cross resistance with other tetracyclines is common.
Antimicrobial Activity
Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)].
Gram-negative Bacteria
Acinetobacter species
Bartonella bacilliformis
Brucella species
Campylobacter fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Klebsiella granulomatis
Klebsiella species
Neisseria gonorrhoeae
Shigella species
Vibrio cholerae
Yersinia pestis

Gram-positive Bacteria
Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae

Anaerobic Bacteria
Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes

Other Bacteria
Nocardiae and other aerobic Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae species
Treponema pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum

Parasites
Balantidium coli
Entamoeba species
Plasmodium falciparum*
*Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.

Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antibacterial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug for treatment.

Dilution techniques:
Quantitative methods are used to determine antibacterial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method5,6,7,8,9 (broth and/or agar). The MIC values should be interpreted according to criteria provided in Table 1.

Diffusion techniques:
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds.

The zone size should be determined using a standardized test method5,7,10. This procedure uses paper disks impregnated with 30 mcg doxycycline to test the susceptibility of bacteria to doxycycline. The disk diffusion interpretive criteria are provided in Table 1.

Anaerobic Techniques:
For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method5,11. The MIC values obtained should be interpreted according to the criteria provided in Table 1.

Doxycycline susceptibility testing interpretive criteria for anaerobes, Haemophilus influenzae, Mycoplasma pneumoniae, Neisseria gonorrhoeae, and Ureaplasma urealyticum have not been established. Isolates of these species that are susceptible to tetracycline are also considered susceptible to doxycycline.5

A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate (I) indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug product is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentration usually achievable at the infection site; other therapy should be selected.

Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test5,6,7,8,9,10,11. Standard doxycycline powders should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg doxycycline disk, the criteria noted in Table 2 should be achieved.

AU: Tetracyclines are considered safe for use during the first 18 weeks of pregnancy (16 weeks postconception); use should be avoided during the second and third trimesters of pregnancy. UK: Use of most oral formulations is contraindicated; use of the 40 mg capsule formulation is contraindicated during the second and third trimesters. US: Use of the IV formulation is not recommended unless considered essential for patient welfare. Most oral formulations of this drug should not be used during pregnancy unless the benefit outweighs the risk; use of the 40 mg capsule formulation is not recommended. AU TGA pregnancy category: D US FDA pregnancy category: -Most products: D -Doryx(R) MPC, Vibramycin(R), Vibra-Tabs(R): Not assigned. Risk summary: Use of this drug in pregnant women may cause fetal harm. Comments: -Use of tetracyclines after the first 18 weeks of pregnancy may affect the formation of the baby's teeth and cause discoloration. -According to some authorities, this drug should be used during tooth development (e.g., last half of pregnancy) only if benefits are expected to outweigh risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), especially if alternative therapies are unavailable. -If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. -According to some authorities, the 40 mg capsule formulation should be stopped at once if the patient becomes pregnant.

Animal studies have revealed evidence of embryofetal toxicity, including toxic effects on skeletal formation. Animal studies indicate this drug crosses the placenta and is found in fetal tissues. There are no controlled data in human pregnancy; most reported human experience was short-term, first trimester exposure but no human data are available assessing long-term therapy during pregnancy (e.g., regimen for anthrax exposure). Congenital defects have been reported with tetracyclines; large doses have caused acute fatty liver necrosis in pregnant women (particularly those with pyelonephritis). Fetal effects may be dose-related. When used during tooth development (second half of pregnancy), tetracyclines may cause permanent yellow-grey-brown discoloration of the teeth; this side effect is more common during prolonged use but has been seen after short-term therapy. Enamel hypoplasia has also been reported. An expert review of data regarding use of this drug during pregnancy by the Teratogen Information System (TERIS) concluded that substantial teratogenic risk from therapeutic doses during pregnancy is unlikely (data quantity and quality limited to fair); insufficient data to state there is no risk. Population-based data from the Hungarian Case-Control Surveillance of Congenital Abnormalities revealed that of 32,804 women who had infants with no defects, 63 (0.19%) were treated with this drug during pregnancy. Of 18,515 women who had infants with congenital abnormalities, 56 (0.3%) were treated with this drug. This study showed a weak but marginally statistically significant association with total malformations and use of this drug anytime during pregnancy. This association was not seen when analysis was limited to maternal therapy during organogenesis (i.e., second and third months of gestation), except for a marginal association with neural tube defect based on 2 exposed cases. Data were based on retrospective recall and did not include alcohol or tobacco usage. In a small prospective study (81 pregnancies), 43 pregnant women were treated with this drug for 10 days during early first trimester. All mothers reported their exposed infants were normal at 1 year of age. In mass casualty settings after release of biological weapons, the Working Group on Civilian Biodefense has recommended this drug as an alternative drug for prophylaxis and treatment of anthrax, tularemia, and plague. The risk of using this drug during pregnancy is outweighed by the high fatality rates from these infections. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Substance Name

Doxycycline

CAS Registry Number

564-25-0

Drug Class

Antiinfective Agents

Antibacterial Agents

Tetracyclines