Targadox

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 ever had:

• liver disease;

• kidney disease;

• asthma or sulfite allergy;

• increased pressure inside your skull; or

• if you also take isotretinoin, seizure medicine, or a blood thinner such as warfarin (Coumadin).

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.

Taking this medicine during pregnancy may affect tooth and bone development in the unborn baby. Taking doxycycline during the last half of pregnancy can cause permanent tooth discoloration later in the baby's life. Tell your doctor if you are pregnant or if you become pregnant while using this medicine.

Doxycycline can make birth control pills less effective. Ask your doctor about using a non-hormonal birth control (condom, diaphragm with spermicide) to prevent pregnancy.

Doxycycline can pass into breast milk and may affect bone and tooth development in a nursing infant. Do not breast-feed while you are taking doxycycline.

Doxycycline can cause permanent yellowing or graying of the teeth in children younger than 8 years old. Children should use doxycycline only in cases of severe or life-threatening conditions such as anthrax or Rocky Mountain spotted fever. The benefit of treating a serious condition may outweigh any risks to the child's tooth development.

• It is used to treat pimples (acne).
• It is used to treat or prevent bacterial infections.
• It is used to prevent malaria.
• It is used to treat swelling of the tissue around the teeth (periodontitis). It is used with scaling and root planing.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to doxycycline or any other part of TargaDOX (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 TargaDOX with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

General

As with other antibacterial drugs, use of doxycycline hyclate tablets may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, doxycycline hyclate tablets should be discontinued and appropriate therapy instituted.

Incision and drainage or other surgical procedures should be performed in conjunction with antibacterial therapy, when indicated.

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.

Prescribing doxycycline hyclate tablets in the absence of 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.

Information for Patients

Patients taking doxycycline for malaria prophylaxis should be advised:

- that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria. - to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (e.g., staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent). - that doxycycline prophylaxis: - should begin 1 to 2 days before travel to the malarious area, - should be continued daily while in the malarious area and after leaving the malarious area, - should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area, - should not exceed 4 months.

All patients taking doxycycline should be advised:

- to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered. (See WARNINGS.) - to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.) - that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. (See DRUG INTERACTIONS.) - that the absorption of tetracyclines is reduced when taking bismuth subsalicylate. (See DRUG INTERACTIONS.) - that the use of doxycycline might increase the incidence of vaginal candidiasis.

Patients should be counseled that antibacterial drugs, including doxycycline hyclate tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline hyclate tablets is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate tablets or other antibacterial drugs in the future.

Diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterials are discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.

Laboratory Tests

In venereal disease, when co-existent syphilis is suspected, dark field examinations should be done before treatment is started and the blood serology repeated monthly for at least 4 months.

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

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 bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin.

Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations.

Absorption of tetracyclines is impaired by bismuth subsalicylate.

Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

The concurrent use of tetracycline and Penthrane® (methoxyflurane) has been reported to result in fatal renal toxicity.

Concurrent use of tetracycline may render oral contraceptives less effective.

Drug/Laboratory Test Interactions

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors).

Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro mammalian cell assays have been reported for related antibacterial drugs (tetracycline, oxytetracycline).

Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.

Pregnancy: Teratogenic Effects. Pregnancy Category D:

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 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 riska. 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 fifty-six (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 (i.e., 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.b

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.c

Nonteratogenic Effects: (See WARNINGS.)

Labor and Delivery

The effect of tetracyclines on labor and delivery is unknown.

Nursing Mothers

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; however, the effects of prolonged exposure to doxycycline in breast milk are unknown.d Because of the potential for serious adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (See WARNINGS.)

Pediatric Use

Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline 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. (See WARNINGS and DOSAGE AND ADMINISTRATION.)

Due to oral doxycycline’s virtually complete absorption, side effects of the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines:

Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Hepatotoxicity has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. (See DOSAGE AND ADMINISTRATION.)

Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS.)

Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS.)

Immune: Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus, and drug rash with eosinophilia and systemic symptoms (DRESS).

Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.

Other: bulging fontanels in infants and intracranial hypertension in adults. (See PRECAUTIONS– General.)

When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function studies are known to occur.

To report SUSPECTED ADVERSE REACTIONS, contact Journey Medical Corporation at 1-877-801-1298, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.

Targadox™ (doxycycline hyclate tablets, USP) equivalent to 50 mg of doxycycline: Light beige color, round convex, film coated tablets debossed “050” below, “J” on one side and plain on the other.

Bottles of 5 tablets NDC 69489-111-05

Bottles of 60 tablets NDC 69489-111-60

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

TARGADOX

(doxycycline hyclate USP) tablets

50 mg

Rx Only

Targadox  doxycycline hyclate tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:69489-111 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DOXYCYCLINE HYCLATE (DOXYCYCLINE ANHYDROUS) DOXYCYCLINE ANHYDROUS 50 mg

Inactive Ingredients Ingredient Name Strength CELLULOSE, MICROCRYSTALLINE   MAGNESIUM STEARATE   HYPROMELLOSES   TITANIUM DIOXIDE   POLYETHYLENE GLYCOLS   FD&C YELLOW NO. 6   POLYSORBATE 80   FD&C BLUE NO. 2

Product Characteristics Color BROWN (Beige) Score no score Shape ROUND Size 7mm Flavor Imprint Code 050;J Contains

Packaging # Item Code Package Description 1 NDC:69489-111-05 5 TABLET in 1 BOTTLE 2 NDC:69489-111-60 60 TABLET in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA062269 08/29/2016

Labeler - Journey Medical Corporation (079640860)

Revised: 08/2016   Journey Medical Corporation