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Tetracyclines (Topical)

This monograph includes information on the following:

1) Chlortetracycline
2) Meclocycline  
3) Tetracycline

VA CLASSIFICATION
Chlortetracycline
Primary: DE101

Meclocycline
Primary: DE752

Tetracycline
Primary: DE752
Secondary: DE101


Commonly used brand name(s): Achromycin3; Aureomycin1; Meclan2; Topicycline3.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antiacne agent (topical)—Meclocycline; Tetracycline Hydrochloride for Topical Solution;

Antibacterial (topical)—Chlortetracycline; Tetracycline Hydrochloride Ointment;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Acne vulgaris(treatment)—Meclocycline sulfosalicylate cream and tetracycline hydrochloride for topical solution are indicated for the topical treatment of acne vulgaris. They may be effective in grades II and III acne, which are characterized by inflammatory lesions such as papules and pustules. {04} {07}

Skin infections, bacterial, minor (treatment)—Chlortetracycline hydrochloride ointment and tetracycline hydrochloride ointment are indicated in the topical treatment of minor skin infections caused by streptococci, staphylococci, and other susceptible organisms. {08}

[Skin infections, bacterial, minor (prophylaxis)] or
[Ulcer, dermal (treatment)]—Topical chlortetracycline and tetracycline hydrochloride ointment are used in the prophylaxis of minor bacterial skin infections and in the treatment of dermal ulcer.

—Not all species or strains of a particular organism may be susceptible to tetracyclines.

Unaccepted
Topical tetracyclines are not effective in deep cystic lesions or in noninflammatory lesions. In addition, topical antibacterials are not generally considered to be as effective as systemic antibacterials in the treatment of acne, especially severe inflammatory acne.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Chlortetracycline hydrochloride: 515.35
    Meclocycline sulfosalicylate: 695.05
    Tetracycline hydrochloride: 480.90

Mechanism of action/Effect:

Antiacne agent (topical)—Probably due to their antibacterial activity. Topical tetracyclines are thought to suppress the growth of Propionibacterium acnes (Corynebacterium acnes) , an anaerobe found in sebaceous glands and follicles. P. acnes produces proteases, hyaluronidases, lipases, and chemotactic factors, all of which can produce inflammatory components or inflammation directly.

Antibacterial (topical)—Tetracyclines are broad-spectrum bacteriostatic agents and act by inhibiting protein synthesis by blocking the binding of aminoacyl tRNA (transfer RNA) to the mRNA (messenger RNA) ribosome complex. Reversible binding occurs primarily at the 30 S ribosomal subunit of susceptible organisms. Bacterial cell wall synthesis is not inhibited.

Absorption:

Meclocycline—Virtually no absorption following topical application to intact skin.

Tetracycline—Vehicle containing n-decyl dimethyl sulfoxide used for topical solution claimed to enhance cutaneous penetration of tetracycline.

Peak serum concentration:

Up to 0.1 mcg per mL following continuous twice-daily application of tetracycline hydrochloride topical solution to skin.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to one tetracycline, tetracycline combination, or tetracycline derivative may be sensitive to other tetracyclines also.

Carcinogenicity


Tetracycline hydrochloride for topical solution:

A two-year dermal study in mice has not shown that tetracycline hydrochloride for topical solution is carcinogenic. {03}


Pregnancy/Reproduction
Fertility—

Meclocycline

Adequate and well-controlled studies in humans have not been done. Studies in rats and rabbits, given oral doses of up to 1000 times the human dose (i.e., 1 gram of cream daily), have not shown that meclocycline causes impaired fertility.



Tetracycline hydrochloride for topical solution

Adequate and well-controlled studies in humans have not been done. Studies in rats and rabbits, given doses of up to 246 times the human dose (i.e., 0.0325 mL per kg of body weight daily), have not shown that tetracycline hydrochloride for topical solution causes impaired fertility.


Pregnancy—

Meclocycline

Adequate and well-controlled studies in humans have not been done.

Studies in rabbits have shown that meclocycline, applied topically, causes a slight delay in ossification. However, studies in rats and rabbits, given oral doses of up to 1000 times the human dose (i.e., 1 gram of cream daily), have not shown that meclocycline causes other adverse effects on the fetus.

FDA Pregnancy Category B. {02}



Tetracycline hydrochloride for topical solution

Adequate and well-controlled studies in humans have not been done.

Studies in rats and rabbits, given doses of up to 246 times the human dose (i.e., 0.0325 mL per kg of body weight daily), have not shown that tetracycline hydrochloride for topical solution causes adverse effects on the fetus.

FDA Pregnancy Category B. {03}



Tetracyclines, other

Problems in humans have not been documented.


Breast-feeding

It is not known whether topical tetracyclines are distributed into breast milk. However, tetracyclines are unlikely to be distributed into breast milk in significant amounts following topical administration, since the total daily dose is small (e.g., less than 5 mg for tetracycline hydrochloride for topical solution) and serum concentrations following topical administration are undetectable or very low (up to 0.1 mcg per mL).

Pediatrics


Tetracycline hydrochloride for topical solution:

Appropriate studies have not been performed in children up to 11 years of age. However, no pediatrics-specific problems have been documented to date in children 11 years of age or older.



Geriatrics


No information is available on the relationship of age to the effects of topical tetracyclines in geriatric patients.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.


For tetracycline hydrochloride for topical solution
Abrasive or medicated soaps or cleansers or
Acne preparations, topical, other or
Alcohol-containing preparations, topical, such as after-shave lotions, astringents, perfumed toiletries, or shaving creams or lotions or
Cosmetics or soaps with a strong drying effect or
Isotretinoin or
Medicated cosmetics or ``cover-ups'' or
Preparations containing peeling agents, topical, such as benzoyl peroxide, resorcinol, salicylic acid, or sulfur    (concurrent use with tetracycline hydrochloride for topical solution may cause a cumulative irritant or drying effect, especially with the application of peeling, desquamating, or abrasive agents, resulting in excessive irritation of the skin)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to tetracyclines


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Pain, redness, swelling, or other sign of irritation not present before therapy



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
For topical solution
    
Dry or scaly skin
    
stinging or burning feeling

For cream and topical solution
    
Faint yellowing of the skin, especially around hair roots






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tetracyclines (Topical).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to tetracycline or to any related antibiotics, such as chlortetracycline, demeclocycline, doxycycline, methacycline, minocycline, or oxytetracycline; allergy to formaldehyde (contained in meclocycline cream)

Proper use of this medication

For all dosage forms
» Compliance with full course of therapy, which may take months or longer

Proper administration technique

May stain clothing

» Proper dosing
Missed dose: Applying as soon as possible; not applying if almost time for next dose

» Proper storage

For cream and topical solution only
» Importance of applying medication to entire affected area

» Not using in eyes, nose, mouth, or on other mucous membranes

For topical solution only
» Not using near heat, open flame, or while smoking

Not using after expiration date

» Explanation of presence of floating plastic plug

Not using medication more often than prescribed

Avoiding too frequent washing of affected areas

For topical ointment only
Not using on deep or puncture wounds or serious burns unless directed by physician

Not for ophthalmic use

Precautions while using this medication

For cream and topical solution only
Checking with physician if no improvement in acne within 6 to 8 weeks

Waiting at least 1 hour before applying any other topical medication for acne

May cause slight yellowing of skin

Fluorescence of treated skin under ``black'' light

Proper use of cosmetics

For topical solution only
Checking with physician if treated skin becomes excessively dry

For topical ointment only
Checking with physician if no improvement within 2 weeks


Side/adverse effects
Signs of potential side effects, especially pain, redness, swelling, or other signs of irritation not present before therapy


General Dosing Information
The treated area(s) may be covered with a gauze dressing if desired (ointment only).

Use of topical antibacterials may lead to skin sensitization, resulting in hypersensitivity reactions with subsequent topical or systemic use of the medication.

In the treatment of acne with meclocycline sulfosalicylate cream or tetracycline hydrochloride for topical solution, noticeable improvement may be seen in 4 to 6 weeks. However, in some patients it may require up to 6 to 8 weeks of treatment before noticeable improvement is seen and up to 8 to 12 weeks before maximum benefit is seen.

CHLORTETRACYCLINE

Summary of Differences
Indications: Indicated as a topical antibacterial.


Topical Dosage Forms

CHLORTETRACYCLINE HYDROCHLORIDE OINTMENT USP

Usual adult and adolescent dose
Antibacterial (topical)
Topical, to the skin, one or two times a day. {08}


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


3% (OTC) [Aureomycin]

Canada—


3% (OTC) [Aureomycin{06}{08}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a collapsible tube or in a well-closed, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • For external use only.
   • Continue medicine for full time of treatment.


MECLOCYCLINE

Summary of Differences
Indications: Indicated in the topical treatment of acne vulgaris.

Side/adverse effects: Faint yellowing of the skin, especially around hair roots.


Additional Dosing Information
See also General Dosing Information.

Meclocycline sulfosalicylate cream may also be effective when applied less frequently (e.g., once a day). However, some reports indicate it is much less effective and improvement may be delayed.


Topical Dosage Forms

MECLOCYCLINE SULFOSALICYLATE CREAM USP

Usual adult and adolescent dose
Antiacne agent (topical)
Topical, to the skin, two times a day, morning and evening. {04}


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


1% (base) (Rx) [Meclan (sodium formaldehyde sulfoxylate)]{04}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container. Protect from light. Protect from freezing.

Auxiliary labeling:
   • For external use only.
   • Continue medicine for full time of treatment.

Note: Explain administration technique.


Additional information:
The cream is compatible with both oil- and water-base systems.


TETRACYCLINE

Summary of Differences
Indications: Indicated as a topical antibacterial (ointment) and in the topical treatment of acne vulgaris (topical solution).

Side/adverse effects: For topical solution—Dry or scaly skin; faint yellowing of the skin, especially around hair roots; stinging or burning feeling.


Additional Dosing Information
See also General Dosing Information.

Twice-daily use of tetracycline hydrochloride for topical solution on the face and neck for acne delivers an average daily dose of 2.9 mg of tetracycline to the skin. When used twice daily on the face and neck as well as other acne-affected areas, the average daily dose delivered to the skin is 4.8 mg.


Topical Dosage Forms

TETRACYCLINE HYDROCHLORIDE OINTMENT USP

Usual adult and adolescent dose
Antibacterial (topical)
Topical, to the skin, one or two times a day.


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


3% (OTC) [Achromycin{01}]

Canada—


3% (OTC) [Achromycin{05}]

Packaging and storage:
Store preferably between 15 and 30 °C (59 and 86 °F). Store in a well-closed container. Protect from freezing.

Auxiliary labeling:
   • For external use only.
   • Continue medicine for full time of treatment.


TETRACYCLINE HYDROCHLORIDE FOR TOPICAL SOLUTION USP

Usual adult and adolescent dose
Antiacne agent (topical)—Topical, to the skin, two times a day, morning and evening. {07}

Usual pediatric dose
Infants and children up to 11 years of age—Dosage has not been established.

Strength(s) usually available
U.S.—


2.2 mg per mL, when reconstituted according to manufacturer's instructions (Rx) [Topicycline (sodium bisulfite) (40% ethanol in diluent)]{07}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect diluent from freezing.

Stability:
After reconstitution, solutions retain their potency for 2 months at controlled room temperature (15 to 30 °C [59 to 86 °F]).

Auxiliary labeling:
   • For external use only.
   • Continue medicine for full time of treatment.
   • Beyond-use date.
   • Keep container tightly closed.
   • Flammable—Keep from heat and flame.

Note: When dispensing, include patient instructions.
Explain the presence of floating plastic plug in the bottle.
Explain administration technique.


Additional information:
The vehicle is a solution of n-decyl methyl sulfoxide and sucrose esters in 40% alcohol.

To maintain an effective concentration of tetracycline hydrochloride, a sufficient amount of 4-epitetracycline hydrochloride is present, which maintains equilibrium between the two.



Revised: 10/27/1993



References
  1. Tetracycline package insert (Achromycin, Lederle—US), PDR 1993: 1223.
  1. Meclocycline package insert (Meclan, Ortho—US), PDR 1988: 1514-5.
  1. Tetracycline package insert (Topicycline, Norwich Eaton—US), PDR 1988: 1484.
  1. Meclocycline package insert (Meclan, Ortho—US), PDR 1993: 1735.
  1. Tetracycline package insert (Achromycin, Lederle—Canada), CPS 1988: 4.
  1. Chlortetracyline package insert (Aureomycin, Lederle—Canada), CPS 1988: 94.
  1. Tetracycline package insert (Topicycline, Norwich Eaton—US), PDR 1993: 1938.
  1. Chlortetracycline package insert (Aureomycin, Lederle—Canada), CPS 1993: 118.
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