Doxycycline Hyclate (Page 3 of 6)

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of doxycycline. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate a causal relationship to drug exposure.

Due to oral doxycycline’s virtually complete absorption, side effects to 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, 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)]. 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 is discussed above [see Warnings and Precautions (5.3) ].

Renal: Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions (5.8) ].

Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and 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 tetracycline [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.

7 DRUG INTERACTIONS

7.1 Anticoagulant Drugs

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

7.2 Penicillin

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

7.3 Antacids and Iron Preparations

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

7.4 Oral Contraceptives

Concurrent use of tetracycline may render oral contraceptives less effective.

7.5 Barbiturates and anti-epileptics

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

7.6 Penthrane

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

7.7 Drug/Laboratory Test Interactions

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects. Pregnancy Category D:

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.1

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

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

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 are unknown4. 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 and Precautions (5.1, 5.6)].

8.4 Pediatric use

Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline hyclate delayed-release 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 [see Warnings and Precautions (5.1, 5.6) and Dosage and Administration (2.1, 2.3)].

8.5 Geriatric use

Clinical studies of doxycycline hyclate delayed-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Doxycycline hyclate delayed-release tablets, USP, 50 mg contain 3 mg (0.131 mEq) of sodium.

Doxycycline hyclate delayed-release tablets, USP, 75 mg contain 4.5 mg (0.196 mEq) of sodium.

Doxycycline hyclate delayed-release tablets, USP, 80 mg contain 4.8 mg (0.209 mEq) of sodium.

Doxycycline hyclate delayed-release tablets, USP, 100 mg contain 6 mg (0.261 mEq) of sodium.

Doxycycline hyclate delayed-release tablets, USP, 150 mg contain 9 mg (0.392 mEq) of sodium.

Doxycycline hyclate delayed-release tablets, USP, 200 mg contain 12 mg (0.522 mEq) of sodium.

10 OVERDOSAGE

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.

11 DESCRIPTION

Doxycycline hyclate delayed-release tablets, for oral administration, contain specially coated pellets of doxycycline hyclate, a broad-spectrum antibacterial synthetically derived from oxytetracycline, in a delayed-release formulation for oral administration.

The structural formula for doxycycline hyclate is:

Chemical Structure
(click image for full-size original)

with a molecular formula of C22 H24 N2 O8 , HCl, ½ C2 H6 O, ½ H2 O and a molecular weight of 512.9. The chemical designation for doxycycline hyclate is [4S(4aR,5S,5aR,6R,12aS)]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6- methyl-1,11-deoxonaphthacene-2-carboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate. Doxycycline hyclate is a yellow crystalline powder soluble in water and in solutions of alkali hydroxides and carbonates. Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form. Inactive ingredients in the tablet formulation are: lactose monohydrate; microcrystalline cellulose; sodium lauryl sulfate; sodium chloride; talc; anhydrous lactose; corn starch; crospovidone; magnesium stearate; cellulosic polymer coating.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.