Tetracycline

Tetracycline is a Tetracycline Derivative belonging to antibiotic/antimicrobial agents.

Tetracycline is an antibiotic used to treat a wide variety of susceptible infections.

Tetracycline incompletely absorbed from the gastrointestinal tract. The bioavailability is approximately 60-80%. Time to peak plasma concentration is approximately 1-4 hours. Tetracycline widely distributed in body tissues and fluids e.g. ascitic, synovial and pleural fluids. Tetracycline crosses the placenta and enters breast milk. The Plasma protein binding is found to be 55-64%. Tetracycline excreted via urine (up to 55% as unchanged drug) and faeces. The elimination half-life is about 8 hours (range: 6-12 hours).

Tetracycline shows common side effects like Diarrhea, nausea, Vomiting, itching of the rectum or vagina, swollen tongue, black or hairy tongue, sore or irritated throat.

Tetracycline is available in the form of Oral Tablet and Oral Capsule.

Tetracycline is available in India, US, Canada, New Zealand, Singapore, France, Spain, Malaysia, Russia, China, Japan, and Australia.

Tetracycline belongs to the antibiotic/antimicrobial agents acts as a Tetracycline Derivative.

Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.

The onset of action of Tetracycline is not clinically established.

The duration of action for Tetracycline is around 1-2 days.

The Tmax of Tetracycline is approximately 2-4 hours (via Oral).

Tetracycline is available in the form of Oral Tablet and Oral Capsule.

Tetracycline tablet is taken orally, usually in divided dose.

Tetracycline is an antibiotic which is used in the treatment of infections in the lungs, reproductive organs, and cholera. Tetracycline may cause teeth discoloration in the children. It may increase the risk of sunburns when exposed to the sunlight.

Tetracycline is a Tetracycline Derivative belonging to antibiotic/antimicrobial agents.

Tetracycline 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.

Tetracycline is approved for use in the following clinical indications

Adult indication

• Acne vulgaris, inflammatory, moderate to severe
• Cholera, treatment
• Syphilis
• Tularemia
• Plague

Although not approved, there have been certain off-label indications. These include

• Helicobacter pylori eradication
• Hidradenitis suppurativa
• Malaria, treatment, uncomplicated
• Pityriasis lichenoides chronica
• Rosacea, moderate to severe or unresponsive to topical therapy

Pediatric indication

● Acne vulgaris (moderate to severe, inflammatory)

● Balantidium coli infection

● Malaria, uncomplicated; treatment

● Syphilis (penicillin-allergic patients)

Adult Dose

• Acne vulgaris, inflammatory, moderate to severe

Oral: 500 mg twice daily. Treatment should ideally be limited to 3 to 4 months to minimize the risk of resistance.

• Cholera, treatment

Oral: 500 mg 4 times daily for 3 days.

• Syphilis

Early syphilis (primary, secondary, and early latent [<1-year duration])

Oral: 500 mg 4 times daily for 14 days.

Late latent syphilis (>1-year duration)

Oral: 500 mg 4 times daily for 28 days

• Tularemia

Oral: 500 mg 4 times daily for at least 14 days.

• Plague

Postexposure prophylaxis

Oral: 500 mg every 6 hours for 7 days.

Treatment, bubonic or pharyngeal

Oral: 500 mg every 6 hours for 10 to 14 days and for at least a few days after clinical resolution.

• Helicobacter pylori eradication

Oral: 500 mg 4 times daily, in combination with standard-dose proton pump inhibitor twice daily, metronidazole 250 mg 4 times daily or 500 mg 3 or 4 times daily, and either bismuth subcitrate 120 to 300 mg 4 times daily or bismuth subsalicylate 300 to 524 mg 4 times daily; continue regimen for 10 to 14 days.

• Hidradenitis suppurativa

Oral: 500 mg twice daily.

• Malaria, treatment, uncomplicated

Oral: 250 mg 4 times daily for 7 days with quinine sulfate (quinine sulfate duration is region specific).

• Pityriasis lichenoides chronica

Oral: 500 mg 4 times daily until lesions subside, followed by 250 mg 4 times daily for ≥1 month.

• Rosacea, moderate to severe or unresponsive to topical therapy

Oral: 250 to 500 mg twice daily.

Pedriatic Dose

● Acne vulgaris (moderate to severe, inflammatory)

Children ≥8 years and Adolescents: Oral: 500 mg twice daily.

● Balantidium coli infection

Children ≥8 years and Adolescents: Oral: 10 mg/kg/dose 4 times daily for 10 days; maximum dose: 500 mg/dose.

● Malaria, uncomplicated; treatment

Children ≥8 years and Adolescents: Oral: 6.25 mg/kg/dose 4 times daily for 7 days; maximum dose: 250 mg/dose. Use in combination with quinine sulfate (quinine sulfate duration is region/species specific).

● Syphilis (penicillin-allergic patients)

Adolescents: Oral: 500 mg 4 times daily. Treat early syphilis (primary, secondary, and early latent) for 14 days and late latent syphilis or latent syphilis of unknown duration for 28 days.

Tetracycline is available in various strengths as 250mg and 500mg.

Tetracycline is available in the form of Oral Tablet and Oral Capsule.

• Dosage Adjustment in Kidney Patient

GFR >50 mL/minute: Administer recommended dose based on indication every 8 to 12 hours.

GFR 10 to 50 mL/minute: Administer recommended dose based on indication every 12 to 24 hours.

GFR <10 mL/minute: Administer recommended dose based on indication every 24 hours.

Serum concentrations may be decreased if taken with dairy products. Management: Take on an empty stomach 1 hour before or 2 hours after meals to increase total absorption.

Tetracycline is contraindicated in patients with

• Hypersensitivity to any of the tetracyclines or any component of the formulation.
• Severe liver disease
• Severe renal disease
• Use in children <12 years of age for therapy of common infections or conditions where bactericidal effect is essential (bacterial endocarditis)
• Surgical prophylaxis
• Pregnancy
• Breastfeeding

• Increased BUN

May be associated with increases in serum urea nitrogen (BUN) secondary to antianabolic effects; use caution in patients with renal impairment.

• Intracranial hypertension (eg, pseudotumor cerebri)

Intracranial hypertension (headache, blurred vision, diplopia, vision loss, and/or papilledema) has been associated with use. Women of childbearing age who are overweight or have a history of intracranial hypertension are at greater risk. Concomitant use of isotretinoin (known to cause pseudotumor cerebri [PTC]) and tetracycline should be avoided. Intracranial hypertension typically resolves after discontinuation of treatment; however, permanent visual loss is possible. If visual symptoms develop during treatment, prompt ophthalmologic evaluation is warranted. Intracranial pressure can remain elevated for weeks after drug discontinuation; monitor patients until they stabilize.

• Photosensitivity

May cause photosensitivity; discontinue if skin erythema occurs. Use skin protection and avoid prolonged exposure to sunlight; do not use tanning equipment.

• Superinfection

Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Tetracyclines are present in the milk of lactating women who are taking a drug in this class. Because of the potential for serious adverse reactions in nursing infants from tetracyclines, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

Animal studies have revealed evidence of embryotoxicity and teratogenicity, including toxic effects on skeletal formation. There are no controlled data in human pregnancy, however, congenital defects and maternal hepatotoxicity have been reported. When used during tooth development (second half of pregnancy) tetracyclines may cause permanent yellow-gray-brown discoloration of the teeth and enamel hypoplasia. The use of tetracycline during pregnancy is generally not recommended, especially during the last half of pregnancy.

Serum concentrations may be decreased if taken with dairy products. Management: Take on an empty stomach 1 hour before or 2 hours after meals to increase total absorption.

• Common

Pericarditis, Erythematous rash, maculopapular rash, skin photosensitivity, Anorexia, Clostridioides difficile-associated diarrhea, diarrhea, dysphagia, enterocolitis, epigastric discomfort, glossitis, melanoglossia, nausea, vomiting, Inflammatory anogenital lesion (with monilial overgrowth), Henoch-Schonlein purpura, Hepatic failure, hepatotoxicity, Serum sickness-like reaction, Exacerbation of systemic lupus erythematosus.

• Rare

Exfoliative dermatitis, nail discoloration, onycholysis, microscopic thyroid discoloration, Discoloration of permanent tooth, dysgeusia, enamel hypoplasia, esophageal ulcer, esophagitis, pancreatitis, Balanitis, Aplastic anemia, eosinophilia, hemolytic anemia, immune thrombocytopenia, neutropenia, thrombocytopenia, Hypersensitivity reaction, nonimmune anaphylaxis, Intracranial hypertension, Abnormal bone growth, lupus-like syndrome, Conjunctival discoloration, Increased blood urea nitrogen.

• Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
• Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
• Antacids: May decrease the absorption of Tetracyclines. Management: Separate administration of antacids and oral tetracycline derivatives by several hours when possible to minimize the extent of this potential interaction. Monitor for decreased therapeutic effects of tetracyclines.
• Atovaquone: Tetracycline (Systemic) may decrease the serum concentration of Atovaquone.
• Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy.
• BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical).
• BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization).
• Bile Acid Sequestrants: May decrease the absorption of Tetracyclines.
• Bismuth Subcitrate: May decrease the serum concentration of Tetracyclines. Management: Avoid administration of oral tetracyclines within 30 minutes of bismuth subcitrate administration. This is of questionable significance for at least some regimens intended to treat H. pylori infections.
• Bismuth Subsalicylate: May decrease the serum concentration of Tetracyclines. Management: Consider dosing tetracyclines 2 hours before or 6 hours after bismuth. The need to separate doses during Helicobacter pylori eradication regimens is questionable.
• Calcium Salts: May decrease the serum concentration of Tetracyclines. Management: If coadministration of oral calcium with oral tetracyclines cannot be avoided, consider separating administration of each agent by several hours.
• Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics.
• Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors.
• Iron Preparations: Tetracyclines may decrease the absorption of Iron Preparations. Iron Preparations may decrease the serum concentration of Tetracyclines. Management: Avoid this combination if possible. Administer oral iron preparations at least 2 hours before, or 4 hours after, the dose of the oral tetracycline derivative. Monitor for decreased therapeutic effect of oral tetracycline derivatives.
• Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol.
• Lanthanum: May decrease the serum concentration of Tetracyclines. Management: Administer oral tetracycline antibiotics at least 2 hours before or after lanthanum.
• Lithium: Tetracyclines may increase the serum concentration of Lithium.
• Magnesium Dimecrotate: May interact via an unknown mechanism with Tetracyclines.
• Magnesium Salts: May decrease the absorption of Tetracyclines. Only applicable to oral preparations of each agent. Management: Avoid coadministration of oral magnesium salts and oral tetracyclines. If coadministration cannot be avoided, administer oral magnesium at least 2 hours before, or 4 hours after, oral tetracyclines. Monitor for decreased tetracycline therapeutic effects.
• Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine.
• Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic).
• Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane.
• Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen.
• Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Tetracyclines. Management: Avoid this combination if possible. If coadministration cannot be avoided, administer the polyvalent cation-containing multivitamin at least 2 hours before or 4 hours after the tetracycline derivative. Monitor for decreased tetracycline effects.
• Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Tetracyclines. Management: If coadministration of a polyvalent cation-containing multivitamin with oral tetracyclines cannot be avoided, administer the polyvalent cation-containing multivitamin either 2 hours before or 4 hours after the tetracycline product.
• Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
• Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins.
• Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
• Quinapril: May decrease the serum concentration of Tetracyclines.
• Quinine: Tetracycline (Systemic) may increase the serum concentration of Quinine.
• Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern.
• Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic.
• Strontium Ranelate: May decrease the serum concentration of Tetracyclines. Management: To minimize any potential impact of strontium ranelate on tetracycline antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during tetracycline therapy.
• Sucralfate: May decrease the absorption of Tetracyclines. Management: Administer most tetracycline derivatives at least 2 hours prior to sucralfate in order to minimize the impact of this interaction. Administer oral omadacycline 4 hours prior to sucralfate.
• Sucroferric Oxyhydroxide: May decrease the serum concentration of Tetracyclines. Management: Administer oral/enteral doxycycline at least 1 hour before sucroferric oxyhydroxide. Specific dose separation guidelines for other tetracyclines are not presently available. No interaction is anticipated with parenteral administration of tetracyclines.
• Sulfonylureas: Tetracyclines may enhance the hypoglycemic effect of Sulfonylureas.
• Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose.
• Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
• Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists.
• Zinc Salts: May decrease the absorption of Tetracyclines. Only a concern when both products are administered orally. Management: Separate administration of oral tetracycline derivatives and oral zinc salts by at least 2 hours to minimize this interaction.

The common side effects of Tetracycline include the following

Common side effects

● Diarrhea, nausea, Vomiting, itching of the rectum or vagina, swollen tongue, black or hairy tongue, sore or irritated throat.

Rare side effects

● Headache, blurred vision, seeing double, or loss of vision, skin rash, hives, swelling of the face, throat, tongue, lips, and eyes, difficulty breathing or swallowing, joint stiffness or swelling, unusual bleeding or bruising, chest pain, a return of fever, sore throat, chills, or other signs of infection, watery or bloody stools, stomach cramps, or fever during treatment or for up to two or more months after stopping treatment.

• Pregnancy

Pregnancy Category D

Animal studies have revealed evidence of embryotoxicity and teratogenicity, including toxic effects on skeletal formation. There are no controlled data in human pregnancy, however, congenital defects and maternal hepatotoxicity have been reported. When used during tooth development (second half of pregnancy) tetracyclines may cause permanent yellow-gray-brown discoloration of the teeth and enamel hypoplasia. The use of tetracycline during pregnancy is generally not recommended, especially during the last half of pregnancy.

• Nursing Mothers

Tetracyclines are present in the milk of lactating women who are taking a drug in this class. Because of the potential for serious adverse reactions in nursing infants from tetracyclines, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

• Pediatric Use

For children above eight years of age: usual daily dose is 10 to 20 mg/lb (25 to 50 mg/kg) body weight divided in four equal doses. Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.

In case of overdosage, treat symptomatically and institute sup- portive measures.

Pharmacodynamic

Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally, tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.

Pharmacokinetics

• Absorption

Tetracycline incompletely absorbed from the gastrointestinal tract. The bioavailability is approximately 60-80%. Time to peak plasma concentration is approximately 1-4 hours.

• Distribution

Tetracycline widely distributed in body tissues and fluids e.g. ascitic, synovial and pleural fluids. Tetracycline crosses the placenta and enters breast milk. The Plasma protein binding is found to be 55-64%.

• Metabolism and Excretion

Tetracycline excreted via urine (up to 55% as unchanged drug) and faeces. The elimination half-life is about 8 hours (range: 6-12 hours).

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