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Pronunciation
(tet ra SYE kleen)
Generic Available (U.S.)
Yes: Capsule
Index Terms
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of susceptible bacterial infections of both gram-positive and gram-negative organisms; also infections due to Mycoplasma, Chlamydia, and Rickettsia; indicated for acne, exacerbations of chronic bronchitis, and treatment of gonorrhea and syphilis in patients who are allergic to penicillin; as part of a multidrug regimen for H. pylori eradication to reduce the risk of duodenal ulcer recurrence
Use: Dental
Treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans (AA); as adjunctive therapy in recurrent aphthous ulcers
Use: Unlabeled
Treatment of periodontitis associated with presence of Actinobacillus actinomycetemcomitans (AA)
Pregnancy Risk Factor
D
Pregnancy Considerations
Tetracyclines cross the placenta, enter fetal circulation, and may cause permanent discoloration of teeth if used during the second or third trimester. Maternal hepatic toxicity has been associated with the use of tetracycline during pregnancy, especially in patients with azotemia or pyelonephritis. Because use during pregnancy may cause fetal harm, tetracycline is classified as pregnancy category D.
Lactation
Enters breast milk/not recommended (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Tetracyclines are excreted in breast milk. Tetracycline binds to calcium. The calcium in the maternal milk will decrease the amount of tetracycline absorbed by the breast-feeding infant. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to tetracycline or any component of the formulation; children <8 years of age; pregnancy
Warnings/Precautions
Concerns related to adverse effects:
• Increased BUN: May be associated with increases in BUN secondary to antianabolic effects; use caution in patients with renal impairment.
• Nephropathy: Outdated drug can cause nephropathy.
• Photosensitivity: May cause photosensitivity; discontinue if skin erythema occurs. Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment.
• Pseudotumor cerebri: Has been (rarely) reported with tetracycline use; usually resolves with discontinuation.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Hepatotoxicity has been reported rarely; risk may be increased in patients with pre-existing hepatic or renal impairment.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Special populations:
• Pediatrics: May cause tissue hyperpigmentation, enamel hypoplasia, or permanent tooth discoloration; use of tetracyclines should be avoided during tooth development (children <8 years of age) unless other drugs are not likely to be effective or are contraindicated.
• Pregnancy: Do not use during pregnancy. In addition to affecting tooth development, tetracycline use has been associated with retardation of skeletal development and reduced bone growth.
Adverse Reactions
Frequency not defined.
Cardiovascular: Pericarditis
Central nervous system: Bulging fontanels in infants, increased intracranial pressure, paresthesia, pseudotumor cerebri
Dermatologic: Exfoliative dermatitis, photosensitivity, pigmentation of nails, pruritus
Gastrointestinal: Abdominal cramps, anorexia, antibiotic-associated pseudomembranous colitis, diarrhea, discoloration of teeth and enamel hypoplasia (young children), esophagitis, nausea, pancreatitis, staphylococcal enterocolitis, vomiting
Hematologic: Thrombophlebitis
Hepatic: Hepatotoxicity
Renal: Acute renal failure, azotemia, renal damage
Miscellaneous: Anaphylaxis, candidal superinfection, hypersensitivity reactions, superinfection
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (moderate)
Drug Interactions
Antacids: May decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification
ARIPiprazole: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a moderate CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
Atovaquone: Tetracycline may decrease the serum concentration of Atovaquone. Risk C: Monitor therapy
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Bile Acid Sequestrants: May decrease the absorption of Tetracycline Derivatives. Risk D: Consider therapy modification
Bismuth: May decrease the serum concentration of Tetracycline Derivatives. Management: Consider dosing tetracyclines 2 hours before, or 6 hours after, bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Bismuth Subsalicylate: May decrease the serum concentration of Tetracycline Derivatives. Management: Consider dosing tetracyclines 2 hours before, or 6 hours after, bismuth subsalicylate. The need to separate doses during Helicobacter pylori eradication regimens is questionable. Risk D: Consider therapy modification
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
Calcium Salts: May decrease the serum concentration of Tetracycline Derivatives. Management: If coadministration of oral calcium with oral tetracyclines can not be avoided, consider separating administration of each agent by several hours. Risk D: Consider therapy modification
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily for adults) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Halofantrine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Halofantrine. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of Tetracycline Derivatives. Only a concern with orally administered products. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Decrease ivacaftor dose to 150 mg daily in patients also receiving moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Tetracycline Derivatives. Management: Administer oral tetracycline antibiotics at least two hours before or after lanthanum. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Lurasidone. Risk D: Consider therapy modification
Magnesium Salts: May decrease the absorption of Tetracycline Derivatives. Only applicable to oral preparations of each agent. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents: Tetracycline Derivatives may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Penicillins: Tetracycline Derivatives may diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Propafenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Propafenone. Risk C: Monitor therapy
Quinapril: May decrease the serum concentration of Tetracycline Derivatives. Management: Separate doses of quinapril and oral tetracycline derivatives by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the tetracycline if these products are used concomitantly. Risk D: Consider therapy modification
Ranolazine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ranolazine. Management: Limit the ranolazine adult dose to a maximum of 500 mg twice daily in patients concurrently receiving moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin, etc.). Risk D: Consider therapy modification
Retinoic Acid Derivatives: Tetracycline Derivatives may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Exceptions: Adapalene; Alitretinoin; Tretinoin (Topical). Risk X: Avoid combination
Salmeterol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Salmeterol. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Sucralfate: May decrease the absorption of Tetracycline Derivatives. Management: Administer the tetracycline derivative at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vilazodone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Vilazodone. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tetracycline Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the absorption of Tetracycline Derivatives. Only a concern when both products are administered orally. Exceptions: Zinc Chloride. Risk D: Consider therapy modification
Zuclopenthixol: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Serum concentrations may be decreased if taken with dairy products. Take on an empty stomach 1 hour before or 2 hours after meals to increase total absorption. Administer around-the-clock to promote less variation in peak and trough serum levels.
Herb/Nutraceutical: Dong quai and St John's wort may also cause photosensitization. Management: Avoid dong quai and St John's wort.
Storage
Outdated tetracyclines have caused a Fanconi-like syndrome (nausea, vomiting, acidosis, proteinuria, glycosuria, aminoaciduria, polydipsia, polyuria, hypokalemia). Protect oral dosage forms from light.
Mechanism of Action
Inhibits bacterial protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane
Pharmacodynamics/Kinetics
Absorption: Oral: 75%
Distribution: Small amount appears in bile
Relative diffusion from blood into CSF: Good only with inflammation (exceeds usual MICs)
CSF:blood level ratio: Inflamed meninges: 25%
Protein binding: ~65%
Half-life elimination: Normal renal function: 8-11 hours; End-stage renal disease: 57-108 hours
Time to peak, serum: Oral: 2-4 hours
Excretion: Urine (60% as unchanged drug); feces (as active form)
Dosage
Usual dosage range:
Children >8 years: Oral: 25-50 mg/kg/day in divided doses every 6 hours
Adults: Oral: 250-500 mg/dose every 6 hours
Indication-specific dosing:
Children ≥8 years: Oral:
Malaria, severe, treatment (unlabeled use): 25 mg/kg/day in divided doses every 6 hours (maximum dose: 250 mg every 6 hours) for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC, 2009).
Malaria, uncomplicated, treatment (unlabeled use): 25 mg/kg/day in divided doses every 6 hours (maximum dose: 250 mg every 6 hours) for 7 days with quinine sulfate. Note: Quinine sulfate duration is region specific; consult CDC for current recommendations (CDC, 2009).
Adults: Oral:
Acne: 250-500 twice daily
Chronic bronchitis, acute exacerbation: 500 mg 4 times/day
Erlichiosis: 500 mg 4 times/day for 7-14 days
Malaria, severe, treatment (unlabeled use): Oral: 250 mg 4 times/day for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC, 2009).
Malaria, uncomplicated, treatment (unlabeled use): Oral: 250 mg 4 times/day for 7 days with quinine sulfate. Note: Quinine sulfate duration is region specific; consult CDC for current recommendations (CDC, 2009).
Peptic ulcer disease: Eradication of Helicobacter pylori: 500 mg 2-4 times/day depending on regimen; requires combination therapy with at least one other antibiotic and an acid-suppressing agent (proton pump inhibitor or H2 blocker)
Periodontitis (unlabeled use): 250 mg every 6 hours until improvement (usually 10 days)
Vibrio cholerae:
500 mg 4 times/day for 3 days
Dosing interval in renal impairment:
Clcr 50-80 mL/minute: Administer every 8-12 hours
Clcr 10-50 mL/minute: Administer every 12-24 hours
Clcr <10 mL/minute: Administer every 24 hours
Dialysis: Slightly dialyzable (5% to 20%) via hemo- and peritoneal dialysis or via continuous arteriovenous or venovenous hemofiltration; no supplemental dosage necessary
Dosing adjustment in hepatic impairment: Use caution; no dosing adjustment required
Dental Usual Dosing
Periodontitis: Adults: Oral: 250 mg every 6 hours until improvement (usually 10 days)
Administration: Oral
Oral should be given on an empty stomach (ie, 1 hour prior to, or 2 hours after meals) to increase total absorption. Administer at least 1-2 hours prior to, or 4 hours after antacid because aluminum and magnesium cations may chelate with tetracycline and reduce its total absorption. Administer around-the-clock to promote less variation in peak and trough serum levels.
Monitoring Parameters
Renal, hepatic, and hematologic function test, temperature, WBC, cultures and sensitivity, appetite, mental status
Test Interactions
False-negative urine glucose with Clinistix®
Dietary Considerations
Take on an empty stomach (ie, 1 hour prior to, or 2 hours after meals). Take at least 1-2 hours prior to, or 4 hours after antacid.
Patient Education
Preferable to take on an empty stomach, 1 hour before or 2 hours after meals. Avoid antacids, iron, or dairy products within 2 hours of taking tetracycline. You may experience photosensitivity, dizziness, lightheadedness, or nausea/vomiting. Report rash or intense itching; yellowing of skin or eyes; fever or chills; watery, bloody, or foul-smelling stool; vaginal itching or discharge; excessive thirst or urination; acute headache; unresolved or persistent diarrhea; respiratory difficulty; if condition does not improve; or worsening of condition. Do not take antidiarrheal medication unless instructed by prescriber.
Geriatric Considerations
The role of tetracycline has decreased because of the emergence of resistant organisms. Doxycycline is the tetracycline of choice when one is indicated because of its better GI absorption, less interactions with divalent cations, longer half-life, and the fact that the majority is cleared by nonrenal mechanisms.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Esophagitis, superinfections, and candidal superinfection. Opportunistic “superinfection” with Candida albicans; tetracyclines are not recommended for use during pregnancy or in children ≤8 years of age since they have been reported to cause enamel hypoplasia and permanent teeth discoloration. The use of tetracyclines should only be used in these patients if other agents are contraindicated or alternative antimicrobials will not eradicate the organism. Long-term use associated with oral candidiasis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Tetracycline may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity although the clinical significance is likely minimal; monitor serum lithium levels
Nursing: Physical Assessment/Monitoring
Assess results of culture and sensitivity tests and patient's allergy history prior to beginning therapy. Monitor for nausea, diarrhea, pericarditis, photosensitivity, rash, opportunistic infection, and hypersensitivity.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral, as hydrochloride: 250 mg, 500 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Tetracycline HCl)
250 mg (100): $14.99
500 mg (100): $19.99
Extemporaneously Prepared
A 25 mg/mL oral suspension may be made using capsules. Empty the contents of six 500 mg capsules into mortar. Add a small amount (~20 mL) of a 1:1 mixture of Ora-Sweet® and Ora-Plus® and mix to a uniform paste; mix while adding the vehicle in geometric proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "refrigerate". Stable 28 days refrigerated.
Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.
References
American Academy of Pediatrics, Committee on Drugs, “Requiem for Tetracyclines,” Pediatrics, 1975, 55(1):142-3.
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Centers for Disease Control and Prevention (CDC), “Guidelines for Treatment of Malaria in the United States,” Treatment Table Update, September 23, 2011. Available at http://www.cdc.gov/malaria/pdf/treatmenttable.pdf
Chey WD and Wong B, “American College of Gastroenterology Guideline on the Management of Helicobacter pylori Infection,” Am J Gastroenterol, 2007 102(8):1808-25.
Coronado BE, Opal SM, and Yoburn DC, “Antibiotic-Induced D-Lactic Acidosis,” Ann Intern Med, 1995, 122(11):839-42.
Cuddihy J, “Case Report of Benign Intra-cranial Hypertension Secondary to Tetracycline,” Ir Med J, 1994, 87(3):90.
Fox SA, Berenyi MR, and Straus B, “Tetracycline Toxicity Presenting as a Multisystem Disease,” Mt Sinai J Med, 1976, 43(2):129-35.
Gardner K, Cox T, and Digre KB, “Idiopathic Intracranial Hypertension Associated With Tetracycline Use in Fraternal Twins: Case Reports and Review,” Neurology, 1995, 45(1):6-10.
Gordon JM and Walker CB, “Current Status of Systemic Antibiotic Usage in Destructive Periodontal Disease,” J Periodontol, 1993, 64(8 Suppl):760-71.
Lee AG, “Pseudotumor Cerebri After Treatment With Tetracycline and Isotretinoin for Acne,” Cutis, 1995, 55(3):165-8.
Maroon JC and Mealy J Jr, “Benign Intracranial Hypertension. Sequel to Tetracycline Therapy in a Child,” JAMA, 1979, 216(9):1479-80.
Rams TE and Slots J, “Antibiotics in Periodontal Therapy: An Update,” Compendium, 1992, 13(12):1130, 1132, 1134.
Sargent E, “Tetracycline for Seal Finger,” JAMA, 1980, 244(5):437.
Seymour RA and Heasman PA, “Pharmacological Control of Periodontal Disease. II. Antimicrobial Agents,” J Dent, 1995, 23(1):5-14
Seymour RA and Heasman PA, “Tetracyclines in the Management of Periodontal Diseases. A Review,” J Clin Periodontol, 1995, 22(1):22-35.
Smilack JD, Wilson WR, and Cockerill FR 3d, “Tetracyclines, Chloramphenicol, Erythromycin, Clindamycin, and Metronidazole,” Mayo Clin Proc, 1991, 66(12):1270-80.
Walters BN and Gubbay SS, “Tetracycline and Benign Intracranial Hypertension: Report of Five Cases,” Br Med J (Clin Res Ed), 1981, 282(6257):19-20.
Wandstrat TL and Phillips J, “Pseudotumor Cerebri Responsive to Acetazolamide,” Ann Pharmacother, 1995, 29(3):318.
Yoshikawa TT, “Antimicrobial Therapy for the Elderly Patient,” J Am Geriatr Soc, 1990, 38(12):1353-72.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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