Tetracycline

J01A - Tetracyclines ATC S01AA09 Small molecule approved 1953 Oral Parenteral Topical Natural product

🧬 Cross-allergy: Tetracyclines

JFDA label: Opticyclin eye ointment

Mechanism of Action

Inhibitor of Bacterial 70S ribosome — Bacterial 70S ribosome inhibitor

Target	Action	Gene / class
Bacterial 70S ribosome efficacy	INHIBITOR

Indications

Approved

Acne
Actinomycosis
Acute intestinal amebiasis
Anthrax
Campylobacter
Cholera
Clostridium
Gram-negative infections
Listeriosis
Ophthalmic infections
Relapsing fever
Respiratory tract infection
Rickettsial infections
Sexually transmitted diseases
Skin and skin structure infections
Urinary tract infections
Vincent infection
Yaws
Zoonotic infections

Off-label

Helicobacter pylori eradication
Malaria
Periodontitis associated with presence of Actinobacillus actinomycetemcomitans

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated.

Bacteria

Organism	Activity	MIC
Campylobacter jejuni/coli	Susceptible	21.0 mg/L
Corynebacterium spp.	Susceptible	2.0 mg/L
Haemophilus influenzae	Susceptible	2.0 mg/L
Haemophilus influenzae	Susceptible	21.0 mg/L
Helicobacter pylori	Susceptible	1.0 mg/L
Moraxella catarrhalis	Susceptible	21.0 mg/L
Neisseria gonorrhoeae	Susceptible	0.5 mg/L
Neisseria meningitidis	Susceptible	21.0 mg/L
Staphylococcus aureus	Susceptible	1.0 mg/L
Staphylococcus spp.	Susceptible	11.0 mg/L
Streptococcus A/B/C/G	Susceptible	11.0 mg/L
Streptococcus pneumoniae	Susceptible	1.0 mg/L
Streptococcus pneumoniae	Susceptible	11.0 mg/L
Staphylococcus aureus	Resistant	2.0 mg/L
Streptococcus pneumoniae	Resistant	2.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	Yes
isBactericidal	0
moaCategory	Protein synthesis inhibitor (30S ribosomal)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	Active efflux (Tet pumps),Ribosomal protection proteins

Contraindications

Source: Curated · Lexicomp

Children under 8 years (permanent tooth discolouration and enamel hypoplasia) Absolute
Hypersensitivity to any of the tetracyclines or any component of the formulation Absolute
Pregnancy (causes discolouration and inhibition of bone growth in foetus) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (2)

Not Known Pericarditis · thrombophlebitis

Nervous system disorders (4)

Not Known Bulging fontanel (infants) · increased intracranial pressure · paresthesia · pseudotumor cerebri

Hepatobiliary disorders (1)

Not Known Hepatotoxicity

Renal and urinary disorders (3)

Not Known Acute renal failure · Azotemia · renal insufficiency

Immune system disorders (2)

Not Known Anaphylaxis · hypersensitivity reaction

Gastrointestinal disorders (11)

Not Known Abdominal cramps · anorexia · dental discoloration (young children) · diarrhea · enamel hypoplasia (young children) · esophagitis · nausea · pancreatitis · pseudomembranous colitis (antibiotic-associated) · staphylococcal enterocolitis · vomiting

Skin and subcutaneous tissue disorders (4)

Not Known Exfoliative dermatitis · nail discoloration · pruritus · skin photosensitivity

Infections and infestations (2)

Not Known Fungal superinfection (candida) · superinfection

Dosing

Source: Lexicomp

Usual dosage range: Oral: 250 to 500 mg every 6 to 12 hours Acne: Oral: Initial dose: 1 g daily in divided doses; reduce gradually to 125 to 500 mg/day once improvement is noted (alternate day or intermittent therapy may be adequate in some patients). Note: The shortest possible duration should be used to minimize development of bacterial resistance; re-evaluate at 3 to 4 months (AAD [Zaenglein 2016]) Helicobacter pylori eradication (off-label use): Oral: American College of Gastroenterology guidelines (Chey 2007; Chey 2017): Bismuth quadruple regimen : 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 mg 4 times daily; continue regimen for 10 to 14 days. Malaria, severe, treatment (off-label use): Oral: 250 mg 4 times daily for 7 days with quinidine gluconate. Note: Quinidine gluconate duration is region specific; consult CDC for current recommendations (CDC 2013). Malaria, uncomplicated, treatment (off-label use): Oral: 250 mg 4 times daily for 7 days with quinine sulfate. Note: Quinine sulfate duration is region specific; consult CDC for current recommendations (CDC 2013). Periodontitis (off-label use): Oral: 250 mg every 6 hours until improvement (usually 10 days) Syphilis, penicillin-allergic patients: Note: Data to support the use of alternatives to penicillin are limited in primary and secondary syphilis and are not well documented in the treatment of latent syphilis (CDC [Workowski 2015]) Early syphilis (primary or secondary infection): 500 mg 4 times daily for 14 days. Latent syphilis (late or of unknown duration): 500 mg 4 times daily for 28 days. Tularemia (mild to moderate): Oral: 500 mg 4 times daily for at least 14 days (IDSA [Stevens 2014]) Vibrio cholerae: Oral: 500 mg 4 times daily for 3 days (Seas 1996)

(For additional information see "Tetracycline: Pediatric drug information") Usual dosage range: Children >8 years and Adolescents: Oral: 25 to 50 mg/kg/day in divided doses every 6 hours Malaria, severe, treatment (off-label use): Children ≥8 years and Adolescents: Oral: 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 2013). Malaria, uncomplicated, treatment (off-label use): Children ≥8 years and Adolescents: Oral: 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 2013).

Refer to adult dosing.

Adults: Manufacturer’s labeling: There are no specific dosage adjustments provided in the manufacturer’s labeling; decrease dose and/or extend dosing interval. Alternative dosing (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 250 mg to 500 mg twice daily to 4 times daily. 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 Children >8 years and Adolescents: There are no specific dosage adjustments provided in the manufacturer’s labeling; decrease dose and/or extend dosing interval.

There are no dosage adjustments provided in the manufacturer’s labeling.

Warnings & Precautions

Source: Lexicomp

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 Clostridium 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 preexisting hepatic or renal impairment.

Renal impairment

Use with caution in patients with renal impairment; dosage adjustment recommended. Special populations:

Pediatric

May cause tissue hyperpigmentation, enamel hypoplasia, or permanent tooth discoloration; use of tetracyclines should be avoided during tooth development (children • 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. Other warnings/precautions:

Appropriate use

Acne: The American Academy of Dermatology acne guidelines recommend tetracycline as adjunctive treatment for moderate and severe acne and forms of inflammatory acne that are resistant to topical treatments. Concomitant topical therapy with benzoyl peroxide or a retinoid should be administered with systemic antibiotic therapy (eg, tetracycline) and continued for maintenance after antibiotic course is completed (AAD [Zaenglein 2016]).

Pregnancy & Lactation

Pregnancy

FDA category D

Avoid

Contraindicated from 2nd trimester onward. T1 probably safe for short courses but amoxicillin preferred

Lactation

Tetracycline is excreted into breast milk (Knowles 1965; Matsuda 1984). According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother. The calcium in the maternal milk is expected to decrease the amount of tetracycline absorbed by the breast-feeding infant (Chung 2002). As a class, tetracyclines have generally been avoided in nursing women due to theo

LactMed: monitor the infant.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C22H24N2O8
Molecular weight	444.44 g/mol
IUPAC name	(4S,4aS,5aS,6S,12aR)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide
CAS	60-54-8
PubChem CID	54675776
InChIKey	`OFVLGDICTFRJMM-WESIUVDSSA-N`
logP	-0.21 (XLogP -2.0)
Polar surface area	181.62 Å²
H-bond acceptors / donors	9 / 6
Drug-likeness (QED)	0.34
Lipinski violations	1

SMILES

CN(C)[C@@H]1C(O)=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)cccc4[C@@](C)(O)[C@H]3C[C@@H]12

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT2 (Inhibitor)OAT3 (Inhibitor)OAT4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)MRP2 (Substrate)OAT2 (Substrate)OAT3 (Substrate)OAT4 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Acitretin	major
Aminolevulinic acid	major
Isotretinoin	major
Lomitapide	major
Methoxyflurane	major
Mipomersen	major
Pexidartinib	major
Tretinoin	major
Typhoid vaccine (live)	major
Vibrio cholerae CVD 103-HgR strain live antigen (live)	major
Vitamin A	major
Activated charcoal	moderate
Aluminum hydroxide	moderate
Aminolevulinic acid (topical)	moderate
Aminophylline	moderate
Amoxicillin	moderate
Ampicillin	moderate
Anisindione	moderate
Asparaginase Erwinia chrysanthemi	moderate
Asparaginase Escherichia coli	moderate
Atovaquone	moderate
Atracurium	moderate
Attapulgite	moderate
Bacampicillin	moderate
Balsalazide	moderate
Bedaquiline	moderate
Benzylpenicillin	moderate
Benzylpenicillin (potassium)	moderate
Benzylpenicillin (sodium)	moderate
Bifidobacterium longum infantis	moderate
Bismuth subcitrate potassium	moderate
Bismuth subgallate	moderate
Bismuth subsalicylate	moderate
Calaspargase pegol	moderate
Calcium Phosphate	moderate
Calcium acetate	moderate
Calcium carbonate	moderate
Calcium chloride	moderate
Calcium citrate	moderate
Calcium glubionate anhydrous	moderate

Showing 40 of 100+.

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Opticyclin eye ointment	Ointment 10 mg/g	5 g tube	Amman Pharmaceutical Indusries	0.780
TETRADAR	Capsule 250 mg	16 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.000
TETRADAR	Capsule 250 mg	20 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	1.250
TETRADAR	Capsule 250 mg	500 cap pack varies	Dar Al Dawa Development and Investment Co Ltd/Jordan	25.000