MINOCIN minocycline hydrochloride, a semisynthetic derivative of tetracycline, is named [4 S -(4(alpha),4a(alpha),5a(alpha),12a(alpha))]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a- tetrahydroxy-1, 11-dioxo-2-naphthacenecarboxamide monohydrochloride.
Each vial, dried by cryodesiccation, contains sterile minocycline HCl equivalent to 100 mg minocycline. When reconstituted with 5 mL of Sterile Water for Injection USP, the pH ranges from 2.0 to 2.8.
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. Minocycline HCl is a tetracycline with antibacterial activity comparable to other tetracyclines with activity against a wide range of gram-negative and gram-positive organisms.
Tube dilution testing: Microorganisms may be considered susceptible (likely to respond to minocycline therapy) if the minimum inhibitory concentration (MIC) is not more than 4 mcg/mL. Microorganisms may be considered intermediate (harboring partial resistance) if the MIC is 4 to 12.5 mcg/mL and resistant (not likely to respond to minocycline therapy) if the MIC is greater than 12.5 mcg/mL.
Susceptibility plate testing: If the Kirby-Bauer method of susceptibility testing (using a 30 mcg tetracycline disc) gives a zone of 18 mm or greater, the bacterial strain is considered to be susceptible to any tetracycline. Minocycline shows moderate in vitro activity against certain strains of staphylococci which have been found resistant to other tetracyclines. For such strains, minocycline susceptibility powder may be used for additional susceptibility testing.
Following a single dose of 200 mg administered intravenously to 10 healthy male volunteers, serum levels ranged from 2.52 to 6.63 mcg/mL (average 4.18), after 12 hours they ranged from 0.82 to 2.64 mcg/mL (average 1.38). In a group of five healthy male volunteers, serum levels of 1.4 to 1.8 mcg/mL were maintained at 12 and 24 hours with doses of 100 mg every 12 hours for three days. When given 200 mg once daily for three days, the serum levels had fallen to approximately 1 mcg/mL at 24 hours. The serum half-life following I.V. doses of 100 mg every 12 hours or 200 mg once daily did not differ significantly and ranged from 15 to 23 hours. The serum half-life following a single 200 mg oral dose in 12 essentially normal volunteers ranged from 11 to 17 hours, in 7 patients with hepatic dysfunction ranged from 11 to 16 hours, and in 5 patients with renal dysfunction from 18 to 69 hours.
Intravenously administered minocycline appears similar to oral doses in excretion. The urinary and fecal recovery of oral minocycline when administered to 12 normal volunteers is one-half to one-third that of other tetracyclines.
MINOCIN is indicated in infections caused by the following microorganisms:
Rickettsiae: (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, tick fevers).
Mycoplasma pneumoniae (PPLO, Eaton agent).
Agents of psittacosis and ornithosis.
Agents of lymphogranuloma venereum and granuloma inguinale.
The spirochetal agent of relapsing fever ( Borrelia recurrentis ).
The following gram-negative microorganisms:
Haemophilus ducreyi chancroid
Yersinia pestis and Francisella tularensis, formerly Pasteurella pestis and Pasteurella tularensis,
Bartonella bacilliformis ,
Vibrio comma and Vibrio fetus,
Brucella species (in conjunction with streptomycin).
Because many strains of the following groups of microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended.
MINOCIN is indicated for treatment of infections caused by the following gram-negative microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
Enterobacter aerogenes (formerly Aerobacter aerogenes ),
Mima species and Herellea species,
Haemophilus influenzae (respiratory infections),
Klebsiella species (respiratory and urinary infections).
MINOCIN is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
Up to 44% of strains of Streptococcus pyogenes and 74% of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive.
For upper respiratory infections due to Group A beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever.
Streptococcus pneumoniae ,
Staphylococcus aureus, skin and soft tissue infections.
Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infection.
When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of infections due to:
Neisseria gonorrhoeae, and Neisseria meningitidis,
Treponema pallidum and Treponema pertenue (syphilis and yaws),
Listeria monocytogenes ,
Bacillus anthracis ,
Fusobacterium fusiforme (Vincent's infection),
In acute intestinal amebiasis, the tetracyclines may be a useful adjunct to amebicides.
MINOCIN minocycline HCl is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral and topical agents.
This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
In the presence of renal dysfunction, particularly in pregnancy, intravenous tetracycline therapy in daily doses exceeding 2 g has been associated with deaths through liver failure.
When the need for intensive treatment outweighs its potential dangers (mostly during pregnancy or in individuals with known or suspected renal or liver impairment), it is advisable to perform renal and liver function tests before and during therapy. Also, tetracycline serum concentrations should be followed.
If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy is prolonged, serum level determinations of the drug may be advisable. This hazard is of particular importance in the parenteral administration of tetracyclines to pregnant or postpartum patients with pyelonephritis. When used under these circumstances, the blood level should not exceed 15 mcg/mL and liver function tests should be made at frequent intervals. Other potentially hepatotoxic drugs should not be prescribed concomitantly.
THE USE OF TETRACYCLINES DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY, AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINES, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema. Studies to date indicate that photosensitivity is rarely reported with MINOCIN minocycline HCl.
The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis.
CNS side effects including light-headedness, dizziness or vertigo have been reported. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually disappear rapidly when the drug is discontinued.
Usage in Pregnancy
(See above about use during tooth development.)
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.
The safety of MINOCIN for use during pregnancy has not been established.
Usage in Newborns, Infants, and Children
(See above about use during tooth development.)
All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
Tetracyclines are present in the milk of lactating women who are taking a drug in this class.
Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility for permanent sequelae exists.
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy should be instituted.
In venereal diseases when coexistent syphilis is suspected, darkfield examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.
In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies should be performed.
All infections due to Group A beta-hemolytic streptococci should be treated for at least ten days.
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.
Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective.
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, pancreatitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, and increases in liver enzymes. Rarely, hepatitis and liver failure have been reported.
These reactions have been caused by both the oral and parenteral administration of tetracyclines.
Skin: and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Fixed drug eruptions, including balanitis, have been rarely reported. Erythema multiforme and rarely Stevens-Johnson syndrome have been reported. Photosensitivity is discussed above. (See . )
Pigmentation of the skin and mucous membranes has been reported.
Tooth discoloration has been reported, rarely, in adults.
Renal Toxicity: in BUN has been reported and is apparently dose related. (See . ) Reversible acute renal failure has been rarely reported.
Hypersensitivity Reactions: Urticaria, angioneurotic edema, polyarthralgia, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus, and rarely, pulmonary infiltrates with eosinophilia have been reported. A transient lupus-like syndrome has also been reported.
Blood: anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.
CNS: (See . ) Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants. (See PRECAUTIONS -- General. ) Headache has also been reported.
Other: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid glands. Very rare cases of abnormal thyroid function have been reported.
Decreased hearing has been rarely reported in patients on MINOCIN.
Note: Rapid administration is to be avoided. Parenteral therapy is indicated only when oral therapy is not adequate or tolerated. Oral therapy should be instituted as soon as possible. If intravenous therapy is given over prolonged periods of time, thrombophlebitis may result.
ADULTS: Usual adult dose: 200 mg followed by 100 mg every 12 hours and should not exceed 400 mg in 24 hours. The cryodesiccated powder should be reconstituted with 5 mL Sterile Water for Injection USP and immediately further diluted to 500 mL to 1,000 mL with Sodium Chloride Injection USP, Dextrose Injection USP, Dextrose and Sodium Chloride Injection USP, Ringer' Injection USP, or Lactated Ringer' Injection USP, but not other solutions containing calcium because a precipitate may form. When further diluted in 500 mL to 1,000 mL compatible solutions (except Lactated Ringers), the pH usually ranges from 2.5 to 4.0. The pH of MINOCIN IV 100 mg in Lactated Ringers 500 mL to 1,000 mL usually ranges from 4.5 to 6.0.
Final dilutions (500 mL to 1,000 mL) should be administered immediately but product and diluents are compatible at room temperature for 24 hours without a significant loss of potency. Any unused portions must be discarded after that period.
For children above eight years of age: Usual pediatric dose: 4 mg/kg followed by 2 mg/kg every 12 hours.
In patients with renal impairment: (See . )
Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
MINOCIN® minocycline HCl Intravenous is supplied as 100 mg vials of sterile cryodesiccated powder.
Product No. NDC 0205-5305-94
Store at Controlled Room Temperature 15-30°C (59-86°F).
LEDERLE PARENTERALS, INC.
Carolina, Puerto Rico 00987
50422-95 Revised January 1995