DOXYCYCLINE HYCLATE CAPSULES, USP

/DOXYCYCLINE HYCLATE CAPSULES, USP
DOXYCYCLINE HYCLATE CAPSULES, USP2018-09-06T09:12:40+00:00

Prescription Drug Name:

DOXYCYCLINE HYCLATE CAPSULES, USP

ID:

1362b9a3-135e-7402-e054-00144ff8d46c

Code:

34391-3

CLINICAL PHARMACOLOGY


id: 1362b9a3-1341-7402-e054-00144ff8d46c
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours decreasing to 1.45 mcg/mL at 24 hours. Excretion of doxycycline by the kidney is about 40%/72 hours in individual with normal function (creatinine clearance about 75 mL/min.). This percentage excretion may fall as low as 1-5%/72 hours in individual with severe renal insufficiency (creatinine clearance below 10 mL/min.). Studies have shown no significant difference in serum half-life of doxycycline (range 18-22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter serum half-life. Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

INDICATIONS AND USAGE


id: 1362b9a3-1346-7402-e054-00144ff8d46c
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline Hyclate Capsules, USP and other antibacterial drugs, doxycycline hyclate capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS


id: 1362b9a3-1349-7402-e054-00144ff8d46c
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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

WARNINGS


id: 1362b9a3-134a-7402-e054-00144ff8d46c
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMENENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is m ore common during long-term use of the drugs, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED. Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline hyclate capsules, 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 antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic 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 antibiotic use not directed against
C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of
C. diffic
i
le, and surgical evaluation should be instituted as clinically indicated.
All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. 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 has also been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. 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. 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 ca occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

ADVERSE REACTIONS


id: 1362b9a3-1357-7402-e054-00144ff8d46c
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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.)
Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus. 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 West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE


id: 1362b9a3-1358-7402-e054-00144ff8d46c
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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.

DOSAGE AND ADMINISTRATION


id: 1362b9a3-1359-7402-e054-00144ff8d46c
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS. Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended. For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used. The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage. When used in streptococcal infections, therapy should be continued for 10 days. Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See
ADVERSE REACTIONS.)
If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment. Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food including milk or carbonated beverage, as required. Uncomplicated urethral, endocervical, or rectal infection in adults caused by
Chlamydia
trachomati
s: 100 mg by mouth twice a day for 7 days.
Nongonococcal urethritis (NGU) caused by
C. trachomatis and
U. urealyticum: 100 mg by mouth twice a day for 7 days.
Syphilis – early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice a day for 2 weeks. Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice a day for 4 weeks. Acute epididymo-orchitis caused by
N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.
Acute epididymo-orchitis caused by
C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.
For the prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1 to 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area. Inhalational anthrax (post-exposure): ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.

HOW SUPPLIED


id: 1362b9a3-135a-7402-e054-00144ff8d46c
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Doxycycline Hyclate Capsule USP, equivalent to 100 mg doxycycline: No. 0 Blue/Blue Opaque Hard Gelatin Capsule Printed “West-ward 3142” in Black Ink.                     Unit dose box of 100 capsules (NDC 0904-0428-61)                     50 capsules (NDC 0904-0428-51)                     500 capsules (NDC 0904-0428-40) Store at 20-25°C (68-77°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.

ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY


id: 1362b9a3-135b-7402-e054-00144ff8d46c
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO
4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.
Minocycline, tetracycline PO
4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl, and tetracycline HCl were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a larger goiter with high radioiodine uptake in rats fed a relatively high iodine diet.
Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

Principal Display Panel


id: 1362b9a3-1361-7402-e054-00144ff8d46c
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

Doxycycline Hyclate Capsules, USP 100mg

14 Capsules

NDC 10544-095-14

DESCRIPTION


id: 1362b9a3-1363-7402-e054-00144ff8d46c
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Doxycycline hyclate is a broad-spectrum antibiotic synthetically derived from oxytetracycline. The structural formula is as follows: with a molecular formula of C
22H
24N
2O
8•H
2O and a molecular weight of 462.46. The chemical designation for doxycycline is 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrate. Doxycycline is a light yellow crystalline powder. Doxycycline hyclate is soluble in water.
Doxycycline has a high degree of lipoid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form. Each capsule for oral administration contains doxycycline hyclate equivalent to 50 mg or 100 mg of doxycycline (anhydrous). Inactive ingredients: lactose monohydrate, microcrystalline cellulose, magnesium stearate. 100 mg gelatin capsule shell contains: FD&C Blue #1, silicon dioxide, sodium lauryl sulfate and titanium dioxide. The printing ink contains: D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, n-Butyl Alcohol, Pharmaceutical Glaze, Propylene Glycol, SDA-3A Alcohol and Synthetic Black Iron Oxide.