Reconstitution and Administration 
Minocycline hydrochloride is administered orally.100,105,116,118 Minocycline has been administered IV,114 but a parenteral preparation no longer is commercially available in the US.
Minocycline hydrochloride capsules,118 pellet-filled capsules,100 or film-coated tablets116 should be administered at least 1 hour before or 2 hours after meals. The manufacturer of Dynacin® capsules states that the capsules may be taken with or without food.105 Although the effect appears to be variable, concomitant administration with food and/or milk can decrease the rate and extent of absorption of minocycline by up to about 27%.100,116,118,127 (See Effect of Food or Milk under Pharmacokinetics: Absorption.)
To reduce the risk of esophageal irritation and ulceration, minocycline hydrochloride capsules and film-coated tablets should be administered with adequate amounts of fluid100,105,116,118 and probably should not be given at bedtime or to patients with esophageal obstruction or compression. The pellet-filled capsules should be swallowed whole.100
Dosage
Dosage of minocycline hydrochloride is expressed in terms of minocycline.100,105,116,118
General Adult Dosage
The usual adult oral dosage of minocycline is 200 mg initially, followed by 100 mg every 12 hours.100,105,116,118 Alternatively, if more frequent doses are preferred, adults may receive 100-200 mg of minocycline initially, followed by 50 mg 4 times daily.100,105,116,118
General Pediatric Dosage
The usual oral dosage of minocycline for children older than 8 years of age is 4 mg/kg initially, followed by 2 mg/kg every 12 hours.100,105,116,118
For information on the use of minocycline hydrochloride for the treatment of periodontitis, see Minocycline (EENT) 52:04.04.
Acne
In the adjunctive treatment of inflammatory acne vulgaris unresponsive to other oral anti-infectives (tetracycline hydrochloride, erythromycin), 50 mg of minocycline has been given orally 1-3 times daily.
Chlamydial Infections
For the treatment of nongonococcal urethritis caused by Chlamydia trachomatis or Ureaplasma urealyticum , the manufacturers state that adults can receive oral minocycline in a dosage of 100 mg every 12 hours for at least 7 days.100,116,118
Doxycycline is the tetracycline recommended by the US Centers for Disease Control and Prevention (CDC) for the treatment of nongonococcal urethritis101 and also is the preferred tetracycline for the presumptive treatment of coexisting chlamydial infections in patients with gonorrhea.101
Gonorrhea and Associated Infections
The manufacturers state that uncomplicated gonorrhea (other than urethritis and anorectal infections in men) may be treated with 200 mg of oral minocycline initially, followed by 100 mg every 12 hours for a minimum of 4 days; follow-up cultures should be done within 2-3 days after completion of therapy.100,105,116,118 For the treatment of uncomplicated gonococcal urethritis in adult males, the manufacturers state that the recommended dosage of oral minocycline is 100 mg every 12 hours for 5 days.100,105,116,118
Tetracyclines are not included in current CDC guidelines for the treatment of gonorrhea,101 and doxycycline is the preferred tetracycline for presumptive treatment of coexisting chlamydial infections in patients with gonorrhea.101
Mycobacterial Infections
Leprosy
For the treatment of multibacillary leprosy† in adults who cannot receive rifampin because of adverse effects, intercurrent disease (e.g., chronic hepatitis), or infection with rifampin-resistant Mycobacterium leprae , the World Health Organization (WHO) recommends supervised administration of a regimen of clofazimine (50 mg daily), ofloxacin (400 mg daily), and minocycline (100 mg daily) given for 6 months, followed by a regimen of clofazimine (50 mg daily) and minocycline (100 mg daily) given for at least an additional 18 months.104,108,109,110
For the treatment of multibacillary leprosy in adults who will not accept or cannot tolerate clofazimine,104,108 the WHO recommends supervised administration of a once-monthly rifampin-based multiple-drug regimen (ROM) that includes rifampin (600 mg once monthly), ofloxacin (400 mg once monthly), and minocycline (100 mg once monthly) given for 24 months.104,110
For the treatment of single-lesion paucibacillary leprosy† in certain patient groups, the WHO currently states that adults may receive a single-dose rifampin-based multiple-drug regimen (ROM) that includes a single 600-mg dose of rifampin, a single 400-mg dose of ofloxacin, and a single 100-mg dose of minocycline.104,109,110
For the treatment of single-lesion paucibacillary leprosy in pediatric patients, the WHO recommends that children 5-14 years of age receive a single 300-mg dose of rifampin, a single 200-mg dose of ofloxacin, and a single 50-mg dose of minocycline.107 Children younger than 5 years of age should receive an appropriately adjusted dose of each drug.107
For additional information on the treatment of leprosy, see Rifampin 8:16.04, Dapsone 8:16.08, and Clofazimine 8:16.08.
Mycobacterium marinum Infections
The manufacturers state that optimum dosage has not been established, but granulomas of the skin caused by Mycobacterium marinum have been successfully treated with 100 mg of oral minocycline every 12 hours for 6-8 weeks.100,105,116,118 The American Thoracic Society (ATS) recommends that oral minocycline be given in a dosage of 100 mg twice daily for at least 3 months for the treatment of cutaneous M. marinum infections and states that a minimum of 4-6 weeks of therapy is necessary to determine whether or not the infection is responding.115
Neisseria meningitidis Infections
N. meningitidis Carriers
To eliminate meningococci from the nasopharynx of asymptomatic Neisseria meningitidis carriers in situations in which the risk of meningococcal meningitis is high, the manufacturers state that 100 mg of oral minocycline may be given every 12 hours for 5 days.100,105,116,118
The CDC and the American Academy of Pediatrics (AAP) currently recommend other anti-infective agents (i.e., rifampin, ceftriaxone, ciprofloxacin) for chemoprophylaxis in close contacts of individuals with invasive meningococcal disease.102,103
Nocardiosis
For the treatment of nocardiosis†, the usual dosage of oral minocycline has been given in conjunction with a sulfonamide for 12-18 months.
Pleural Effusions
When used intrapleurally† as a sclerosing agent to control pleural effusions associated with metastatic tumors†, 300 mg of minocycline reportedly has been diluted with 40-50 mL of 0.9% sodium chloride injection and instilled into the pleural space through a thoracostomy tube, followed by clamping of the tube and subsequent removal of the fluid.
Rheumatoid Arthritis
When used in the management of rheumatoid arthritis†, adults have received oral minocycline in a dosage of 100 mg twice daily.111,112,113 A benefit may be evident 1-3 months after initiation of minocycline therapy.111
Syphilis
The manufacturers state that the usual dosage of oral minocycline may be given for 10-15 days for the treatment of syphilis; close follow-up and laboratory tests are recommended.100,105,116,118
Parenteral penicillin G is the drug of choice for all stages of syphilis and doxycycline or tetracycline hydrochloride are the tetracyclines recommended by the CDC for the treatment of primary, secondary, latent, or tertiary syphilis in nonpregnant adults, adolescents, and children 8 years of age or older who are hypersensitive to penicillin.101
Vibrio Infections
Cholera
For the treatment of cholera in conjunction with fluid and electrolyte replacement, an initial 200-mg oral dose of minocycline has been given followed by 100-mg oral doses every 12 hours for 48-72 hours.
Dosage in Renal Impairment
In patients with renal impairment, doses and/or frequency of administration of minocycline should be decreased in response to the degree of impairment.105,116 Some manufacturers state that dosage of oral minocycline should not exceed 200 mg daily in patients with impaired renal function.100,118
Pharmacokinetics
In all studies described in the Pharmacokinetics section, minocycline was administered as the hydrochloride salt.
Absorption
Approximately 90-100% of an oral dose of minocycline hydrochloride is absorbed from the GI tract in fasting adults. Peak serum concentrations usually are attained within 1-4 hours.100,105,116,118
Following oral administration of a single 200-mg dose of minocycline powder- or pellet-filled capsules in fasting adults with normal renal function, peak serum concentrations of the drug are attained within 1-4 hours (average 2.1 hours) and range from 2.1-5.1 mcg/mL (average 3.5 mcg/mL).100,118 In one study in adults with normal renal function given an initial 200-mg oral dose of minocycline as powder-filled capsules followed by 100-mg oral doses every 12 hours, steady-state serum concentrations of minocycline averaged 2.3-3.5 mcg/mL.
Following oral administration of a single 100-mg dose of minocycline as tablets in healthy, fasting adults, peak serum concentrations were attained in 1-3 hours (average 1.7 hours) and ranged from 0.5-1.3 mcg/mL (average 0.8 mcg/mL).116
Because tetracyclines readily chelate divalent or trivalent cations including aluminum, calcium, iron, and magnesium, concurrent oral administration of antacids or other drugs containing these cations may decrease oral absorption of minocycline hydrochloride. (See Drug Interactions in the Tetracyclines General Statement 8:12.24.)
Effect of Food or Milk
Food and/or milk can decrease the rate and extent of absorption of oral minocycline hydrochloride.100,116,127
In one study in healthy adults, administration of a single 100-mg dose of minocycline with food resulted in a 13% decrease in the area under the plasma concentration-time curve (AUC) of the drug compared with administration with water.127 When the same dose was administered with milk, there was a 27% decrease in the AUC compared with administration with water.127
When healthy adults received pellet-filled capsules of minocycline following a standardized meal containing dairy products, peak plasma minocycline concentrations were decreased 11.2% and delayed by approximately 1 hour compared with administration in the fasting state;100 however, the extent of absorption (as represented by the AUC) was similar in fed and fasting individuals.
When minocycline hydrochloride tablets were given concomitantly with a meal containing dairy products, there was a 12% decrease in peak plasma concentrations, a 1-hour delay in peak concentrations, and a 6% decrease in the extent of absorption of the drug.116
Elimination
The serum half-life of minocycline is 11-26 hours in adults with normal renal function.100,105,116,118 In one study, the half-life was reported to be about 17 hours after a single dose and 21 hours after multiple doses.
In a limited number of patients with hepatic dysfunction, the serum half-life of minocycline reportedly ranged from 11-16 hours.100,105,116,118 Although results of studies using minocycline in patients with renal impairment are conflicting, most studies indicate that the serum half-life of the drug is not significantly affected by alterations in renal function. In patients with severe renal impairment, the serum half-life of minocycline is generally reported to be 12-30 hours following single or multiple doses.
In patients with normal renal function, approximately 4-19% of a single oral dose of minocycline is excreted in urine and 20-34% is excreted in feces within 72 hours as active drug. Some studies indicate that minocycline, unlike other currently available tetracyclines, is partially metabolized to at least 6 metabolites.
Chemistry and Stability
Chemistry
Minocycline is a semisynthetic tetracycline antibiotic derived from tetracycline.100,105,118 Minocycline is commercially available as the hydrochloride salt in capsules,105,118 pellet-filled capsules,100 or film-coated tablets.116 Minocycline hydrochloride occurs as a yellow, crystalline powder and is soluble in water and slightly soluble in alcohol.
Stability
Minocycline hydrochloride capsules,105,118 pellet-filled capsules,100 or film-coated tablets,116 should be stored at a controlled room temperature of 20-25°C. These preparations should be protected from light, moisture, and excessive heat.100,105,116,118
Additional Information
For further information on chemistry and stability, mechanism of action, spectrum, resistance, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of minocycline hydrochloride, see the Tetracyclines General Statement 8:12.24. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Only references cited for selected revisions after 1984 are available electronically.
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