Dynacin

DYNACIN- minocycline hydrochloride capsule
MEDICIS, The Dermatology Company

Rx Only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of minocycline hydrochloride capsules and other antibacterial drugs, minocycline hydrochloride capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Minocycline hydrochloride, a semisynthetic derivative of tetracycline, is 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride. The structural formula is represented below:

C₂₃ H₂₇ N₃ O₇ .HCl M. W. 493.94

Each minocycline hydrochloride capsule, for oral administration, contains the equivalent of 50 mg, 75 mg or 100 mg of minocycline. In addition each capsule contains the following inactive ingredients: magnesium stearate and starch (corn).

The 50 mg, 75 mg and 100 mg capsule shells contain: gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide.

The 75 mg and 100 mg capsule shells also contain: black iron oxide.

CLINICAL PHARMACOLOGY

Following oral administration of minocycline hydrochloride capsules, absorption from the gastrointestinal tract is rapid. Maximum serum concentrations following a single dose of minocycline hydrochloride to normal fasting adult volunteers were attained in 1 to 4 hours. The serum half-life in normal volunteers ranges from approximately 11 hours to 22 hours.

When minocycline hydrochloride capsules were given concomitantly with a meal which included dairy products, the extent of absorption of minocycline hydrochloride capsules was not noticeably influenced. The peak plasma concentrations were slightly decreased and delayed by one hour when administered with food, compared to dosing under fasting conditions.

In previous studies with other minocycline dosage forms, the minocycline serum half-life ranged from 11 to 16 hours in 7 patients with hepatic dysfunction, and from 18 to 69 hours in 5 patients with renal dysfunction. The urinary and fecal recovery of minocycline when administered to 12 normal volunteers is one-half to one-third that of other tetracyclines.

Microbiology

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including minocycline, have a similar antimicrobial spectrum of activity against a wide range of gram-positive and gram-negative organisms. Cross-resistance of these organisms to tetracyclines is common.

Minocycline has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

AEROBIC GRAM-POSITIVE MICROORGANISMS

Because many strains of the following gram-positive microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended. Tetracycline antibiotics should not be used for streptococcal diseases unless the organism has been demonstrated to be susceptible. Tetracyclines are not the drug of choice in the treatment of any type of staphylococcal infection.

Bacillus anthracis ^†

Listeria monocytogenes ^†

Staphylococcus aureus

Streptococcus pneumoniae

AEROBIC GRAM-NEGATIVE MICROORGANISMS

Bartonella bacilliformis

Brucella

species

Calymmatobacterium granulomatis

Campylobacter fetus

Francisella tularensis

Haemophilus ducreyi

Vibrio cholerae

Yersinia pestis

Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility tests are especially recommended:

Acinetobacter

species

Enterobacter aerogenes

Escherichia coli

Haemophilus influenzae

Klebsiella

species

Neisseria gonorrhoeae ^†

Neisseria meningitidis ^†

Shigella

species

“OTHER” MICROORGANISMS

Actinomyces

species^†

Borrelia recurrentis

Chlamydia psittaci

Chlamydia trachomatis

Clostridium

species^†

Entamoeba

species

Fusobacterium nucletum

ssp. fusiforme ^†

Mycobacterium marinum

Mycoplasma pneumonia

Propionibacterium acnes

Rickettsiae

Treponema pallidum

subspecies pallidum ^†

Treponema pallidum

subspecies pertenue ^†

Ureaplasma urealyticum

^† When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of infections caused by the cited microorganisms.

Susceptibility tests

Susceptibility testing should be performed with tetracycline since it predicts susceptibility to minocycline. However, certain organisms (e.g., some staphylococci, and Acinetobacter ssp.) may be more susceptible to minocycline and doxycycline than to tetracycline.

Dilution techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method^1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of tetracycline powder. The MIC values should be interpreted according to the following criteria:

For testing aerobic gram-negative microorganisms (Enterobacteriaceae), Acinetobacter ssp. and Staphylococcus aureus.

MIC (µg/mL)	Interpretation
≤ 4.0	Susceptible (S)
8.0	Intermediate (I)
≥16.0	Resistant (R)

For testing Haemophilus influenzae ^a and Streptococcus pneumoniae ^b:

MIC (µg/mL)	Interpretation
≤ 2.0	Susceptible (S)
4.0	Intermediate (I)
≥ 8.0	Resistant (R)

^a These interpretative standards are applicable only to broth microdilution susceptibility testing with Haemophilus influenzae using Haemophilus Test Medium. ¹

^b These interpretative standards are applicable only to broth microdilution susceptibility testing using cation-adjusted Muller-Hinton broth with 2 – 5% lysed horse blood. ¹

For testing Neisseria gonorrhoeae ^c.

MIC (µg/mL)	Interpretation
≤ 0.25	Susceptible (S)
0.5–1.0	Intermediate (I)
≥ 2.0	Resistant (R)

^c These interpretative standards are applicable only to agar dilution susceptibility testing using GC agar base and 1% defined growth supplements. ¹