Minocycline Hydrochloride

Minocycline hydrochloride, a semi synthetic derivative of tetracycline, is [4S(4α,4aα,5aα,12aα)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12atetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide mono hydrochloride. The structural formula is represented below:

C23H27N3O7•HCl        M. W. 493.95

SOLODYN Tablets for oral administration contain minocycline hydrochloride USP equivalent to 55 mg, 65 mg, 80 mg, 105 mg, or 115 mg of minocycline. In addition, 55 mg, 65 mg, 80 mg, 105 mg, and 115 mg tablets contain the following inactive ingredients: lactose monohydrate NF, hypromellose type 2910 USP, magnesium stearate NF, colloidal silicon dioxide NF, and carnauba wax NF. The 55 mg tablets also contain Opadry II Pink which contains: hypromellose type 2910 USP, titanium dioxide USP, lactose monohydrate NF, polyethylene glycol 3350 NF, triacetin USP, and FD&C Red #40. The 65 mg tablets also contain Opadry II Blue which contains: hypromellose type 2910 USP, lactose monohydrate NF, FD&C Blue #1, polyethylene glycol 3350 NF, FD&C Blue #2, titanium dioxide USP, triacetin USP, and D&C Yellow #10. The 80 mg tablets also contain Opadry II Gray which contains: hypromellose type 2910 USP, lactose monohydrate NF, polyethylene glycol 3350 NF, FD&C Blue #2, FD&C Red #40, titanium dioxide USP, triacetin USP, and FD&C Yellow #6. The 105 mg tablets also contain Opadry II Purple which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, D&C Red #27, polyethylene glycol 3350 NF, triacetin USP, and FD&C Blue #1. The 115 mg tablets also contain Opadry II Green which contains: hypromellose type 2910 USP, lactose monohydrate NF, D&C Yellow #10, triacetin USP, FD&C Blue #1, titanium dioxide USP, and FD&C Blue #2.

Indication

SOLODYN is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.

Limitations of Use

SOLODYN did not demonstrate any effect on non-inflammatory acne lesions. Safety of SOLODYN has not been established beyond 12 weeks of use. This formulation of minocycline has not been evaluated in the treatment of infections [see Clinical Studies].

To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, SOLODYN should be used only as indicated [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.

The following table summarizes selected adverse reactions reported in clinical trials at a rate of ≥ 1% for SOLODYN.

Table 2: Selected Treatment-Emergent Adverse Reactions in at least 1% of Clinical Trial Subjects

Postmarketing Experience

Adverse reactions that have been reported with minocycline hydrochloride use in a variety of indications include:

Skin and hypersensitivity reactions: fixed drug eruptions, balanitis, erythema multiforme, Stevens-Johnson syndrome, anaphylactoid purpura, photosensitivity, pigmentation of skin and mucous membranes, hypersensitivity reactions, angioneurotic edema, anaphylaxis, DRESS syndrome [see WARNINGS AND PRECAUTIONS].

Autoimmune conditions: polyarthralgia, pericarditis, exacerbation of systemic lupus, pulmonary infiltrates with eosinophilia, transient lupus-like syndrome.

Central nervous system: pseudotumor cerebri, bulging fontanels in infants, decreased hearing.

Endocrine: brown-black microscopic thyroid discoloration, abnormal thyroid function. Oncology: thyroid cancer.

Oral: glossitis, dysphagia, tooth discoloration.

Gastrointestinal: enterocolitis, pancreatitis, hepatitis, liver failure.

Renal: reversible acute renal failure.

Hematology: hemolytic anemia, thrombocytopenia, eosinophilia.

Preliminary studies suggest that use of minocycline may have deleterious effects on human spermatogenesis [see Nonclinical Toxicology].

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.c 116

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.c 116 Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.a c 116

Acinetobacter Infections

Alternative to imipenem or meropenem for treatment of infections caused by Acinetobacter.c 116 f

Acne

Adjunctive treatment of moderate to severe inflammatory acne.c 116 Not indicated for treatment of noninflammatory acne.a

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;c 116 oral tetracyclines (usually doxycycline or tetracycline) used as follow-up after initial parenteral penicillin G.i

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.c 116 Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.i

Anthrax

Alternative to doxycycline for postexposure prophylaxis to reduce the incidence or progression of disease following a suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax).g Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline;g doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.g

Alternative to doxycycline for treatment of inhalational anthrax when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting).c 116 g A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.g

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.c 116

Brucellosis

Treatment of brucellosis;c 116 tetracyclines (usually doxycycline or tetracycline) considered drugs of choice.f i Tetracyclines used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),c 116 i especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).i

Campylobacter Infections

Treatment of infections caused by Campylobacter.c 116 Tetracyclines (usually doxycycline) are alternatives,i not drugs of choice for C. jejuni.f i

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.c 116 Not included in CDC recommendations for treatment of chancroid.101

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.c 116 Doxycycline is the preferred tetracycline for treatment of these infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.101

Treatment of trachoma and inclusion conjunctivitis caused by C. trachomatis.c 116 Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.c 116

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.c 116 Doxycycline is the preferred tetracycline for these infections.101

Treatment of psittacosis (ornithosis) caused by C. psittaci.c 116 Doxycycline and tetracycline are drugs of choice.a i For initial treatment of severely ill patients, use IV doxycycline.a

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.c 116 Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.f

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.c 116 Should only be used for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffectivea and when in vitro susceptibility tests indicate the organism is susceptible.a c 116

Fusobacterium Infections

Alternative to penicillin G for treatment of infections caused by Fusobacterium fusiforme (Vincent’s infection).c 116

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea (including urethritis) caused by susceptible Neisseria gonorrhoeae.c 116 Tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.101 a

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.c 116 Doxycycline is the tetracycline recommended as drug of choice by CDC.101

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.c 116 Not usually considered a drug of choice or alternative for these infections.f i

Malaria

Other tetracyclines (doxycycline) used for prevention of malaria; data insufficient to evaluate efficacy of minocycline for malaria prevention.117 CDC recommends that individuals receiving long-term minocycline therapy (e.g., for acne) who also require doxycycline malaria prophylaxis should discontinue minocycline 1–2 days prior to travel and initiate doxycycline for such prophylaxis;117 minocycline can be reinitiated after doxycycline malaria prophylaxis is finished.117

Mycobacterial Infections

Alternative for use in multiple-drug regimens for treatment of multibacillary leprosy†.104 107 108 109 110 WHO recommends minocycline as an alternative for multibacillary leprosy regimens in patients who will not accept or cannot tolerate clofazimine104 110 and when rifampin cannot be used because of adverse effects, intercurrent disease (e.g., chronic hepatitis), or infection with rifampin-resistant Mycobacterium leprae.104 110

Component of a single-dose rifampin-based multiple-drug regimen (ROM) for treatment of single-lesion paucibacillary leprosy† (i.e., a single skin lesion with definite loss of sensation but without nerve trunk involvement).104 107 108 109 110 A ROM regimen of a single dose of rifampin, single dose of ofloxacin, and single dose of minocycline is recommended by WHO as an acceptable and cost-effective alternative regimen in antileprosy programs that have detected a large number of patients (e.g., more than 1000 annually) with single-lesion paucibacillary leprosy.104 107 108 109 110

Treatment of cutaneous infections caused by M. marinum;115 c 116 f a drug of choice.115 f

Neisseria meningitidis Infections

Elimination of nasopharyngeal carriage of Neisseria meningitidis.c 116 CDC and AAP recommend use of rifampin, ceftriaxone, or ciprofloxacin for such carriers and no longer recommend use of minocycline.102 103 i

Should not be used for treatment of infections caused by N. meningitidis.c 116

Nocardiosis

Tetracyclines are alternative to co-trimoxazole for treatment of nocardiosis† caused by Nocardia.f

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.c 116 Doxycycline usually is the tetracycline of choice for NGU.101

Consider that some cases of recurrent urethritis following treatment may be caused by tetracycline-resistant U. urealyticum.101

Plague

Treatment of plague caused by Yersinia pestis.c 116 Regimen of choice is streptomycin or gentamicin;f i l alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.i l

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.c 116 Tetracyclines are drugs of choice.f

Rheumatoid Arthritis

Treatment of rheumatoid arthritis†.111 112 113 One of several disease-modifying antirheumatic drugs (DMARDs) that can be used when DMARD therapy is appropriate.111

Rickettsial Infections

Treatment of rickettsial infections including Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.c 116 Doxycycline is the drug of choice for most rickettsial infections.a i f m

Stenotrophomonas maltophilia Infections

Treatment of infections caused by Stenotrophomonas maltophilia†.f j Alternative to co-trimoxazole.f

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.c 116 Doxycycline and tetracycline are the preferred tetracyclines in patients hypersensitive to penicillins.101 Use tetracyclines only if compliance and follow-up can be ensured since efficacy not well documented.101

Tularemia

Treatment of tularemia caused by Francisella tularensis.c 116 Tetracyclines (usually doxycycline) considered alternatives to streptomycin (or gentamicin);f h i risk of relapse and primary treatment failure may be higher than with aminoglycosides.h

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.c 116 Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.c 116 i

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.c 116

• Advise patients that antibacterials (including minocycline) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).c 116

• Importance of completing full course of therapy, even if feeling better after a few days.c 116

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with minocycline or other antibacterials in the future.c 116

• Importance of drinking sufficient quantities of fluids when taking capsules or tablets to reduce the risk of esophageal irritation and ulceration.a

• Advise patients that absorption of some minocycline preparations may be reduced when taken with foods, especially those containing calcium, and that pellet-filled capsules or tablets should be taken at least 1 hour before or 2 hours after meals and/or milk.c 116

• Advise patients that adverse CNS effects (light-headedness, dizziness, vertigo) may occur and caution should be used when driving vehicles or operating hazardous machinery.100 105

• Advise patients to avoid excessive sunlight or artificial UV light and to discontinue the drug at the first sign of skin erythema;a c 116 consider use of sunscreen or sunblock.a

• Advise patients that minocycline may decrease effectiveness of oral contraceptives and that alternative nonhormonal contraceptive measures should be used.a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.c 116 (See Fetal/Neonatal Morbidity under Cautions.)

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs.c 116

• Importance of informing patients of other important precautionary information. (See Cautions.)