MINOCIN ® Minocycline For Injection 100 Mg/Vial

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MINOCIN ^® (minocycline) for Injection and other antibacterial drugs, MINOCIN ^® (minocycline) for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

MINOCIN (minocycline) for Injection, is a sterile formulation of a semisynthetic derivative of tetracycline. The chemical name of minocycline 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.

Its structural formula is:

C ₂₃H ₂₇N ₃O ₇•HCl   M.W. 493.94

MINOCIN is supplied as a sterile yellow to amber lyophilized powder for intravenous infusion. Each vial contains minocycline HCl equivalent to 100 mg minocycline, 269 mg magnesium sulfate heptahydrate (2.2 mEq of magnesium) (an inactive ingredient) and sodium hydroxide (to adjust pH). When reconstituted with 5 mL of Sterile Water for Injection USP the pH ranges from 4.5 to 5.0.

Following a single dose of Minocin 200 mg administered intravenously to 10 healthy male subjects, serum concentrations of minocycline ranged from 2.52 to 6.63 mcg/mL (average 4.18 mcg/mL) at the end of infusion and 0.82 to 2.64 mcg/mL (average 1.38 mcg/mL) after 12 hours. In a group of 5 healthy male subjects, serum concentrations of minocycline ranged from 1.4 to1.8 mcg/mL at the end of the dosing interval following administration of Minocin 100 mg every 12 hours for three days. When Minocin 200 mg once daily was administered for three days, serum concentrations of minocycline were approximately 1 mcg/mL at 24 hours. The serum elimination half-life of minocycline following administration of either Minocin 100 mg every 12 hours or 200 mg once daily was not significantly different and ranged from 15 to 23 hours. The serum elimination half-life of minocycline ranged from 11 to 16 hours in subjects with hepatic impairment (n=7) and 18 to 69 hours in subjects with renal impairment (n=5). In comparison, the serum elimination half-life of minocycline ranged from 11 to 17 hours following a single dose of oral minocycline 200 mg in healthy subjects (n=12).

MINOCIN ^® Intravenous is indicated in the treatment of the following infections due to susceptible isolates of the designated bacteria:

Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers caused by rickettsiae.
Respiratory tract infections caused by Mycoplasma pneumoniae.
Lymphogranuloma venereum caused by Chlamydia trachomatis.
Psittacosis (Ornithosis) due to Chlamydophila psittaci.
Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis caused by Chlamydia trachomatis.
Nongonococcal urethritis, endocervical, or rectal infections in adults caused by Ureaplasma urealyticum or Chlamydia trachomatis.
Relapsing fever due to B orrelia recurrentis. Plague due to Yersinia pestis.
Tularemia due to Francisella tularensis.
Cholera caused by Vibrio cholerae.
Campylobacter fetus infections caused by Campylobacter fetus.
Brucellosis due to Brucella species (in conjunction with streptomycin).
Bartonellosis due to Bartonella bacilliformis.
Granuloma inguinale caused by Klebsiella granulomatis.

Minocycline is indicated for the treatment of infections caused by the following Gram-negative bacteria when bacteriologic testing indicates appropriate susceptibility to the drug:

Escherichia coli.
Enterobacter aerogenes.
Shigella species.
Acinetobacter species.
Respiratory tract infections caused by Haemophilus influenzae.
Respiratory tract and urinary tract infections caused by Klebsiella species.

MINOCIN ^® Intravenous is indicated for the treatment of infections caused by the following Gram-positive bacteria when bacteriologic testing indicates appropriate susceptibility to the drug:

Upper respiratory tract infections caused by Streptococcus pneumoniae.
Skin and skin structure infections caused by Staphylococcus aureus (Note: Minocycline is not the drug of choice in the treatment of any type of staphylococcal infection.)

When penicillin is contraindicated, minocycline is an alternative drug in the treatment of the following infections:

Meningitis due to Neisseria meningitidis.
Syphilis caused by Treponema pallidum subspecies pallidum.
Yaws caused by Treponema pallidum subspecies pertenue.
Listeriosis due to L isteria monocytogenes.
Anthrax due to Bacillus anthracis.
Vincent’s infection caused by Fusobacterium fusiforme.
Actinomycosis caused by Actinomyces israelii.
Infections caused by Clostridium species.

In acute intestinal amebiasis, minocycline may be a useful adjunct to amebicides.

In severe acne, minocycline may be useful adjunctive therapy.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MINOCIN ^® (minocycline) for Injection and other antibacterial drugs, MINOCIN ^® (minocycline) for Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation.

Tooth Development
MINOCIN, like other tetracycline-class antibacterials, can cause fetal harm when administered to a pregnant woman. If any tetracycline is used during pregnancy, or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus. The use of drugs of the tetracycline class 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. Tetracycline drugs, therefore, should not be used during tooth development unless other drugs are not likely to be effective or are contraindicated.

Skeletal Development
All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

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 been noted in animals treated early in pregnancy.

Dermatologic Reaction
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) including fatal cases have been reported with minocycline use. If this syndrome is recognized, the drug should be discontinued immediately.

Anti‑anabolic Action
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. Under such conditions, monitoring of creatinine and BUN is recommended, and the total daily dosage should not exceed 200 mg in 24 hours (See DOSAGE AND ADMINISTRATION). If renal impairment exists, even usual oral or parenteral doses may lead to systemic accumulation of the drug and possible liver toxicity.

Photosensitivity
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported with minocycline.

Central Nervous System Effects
Central nervous system 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.

Clostridium difficile Associated Diarrhea
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including MINOCIN ^®, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Intracranial Hypertension
Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including Minocin. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and Minocin should be avoided because isotretinoin is also known to cause pseudotumor cerebri.

Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.

The following adverse reactions have been observed in patients receiving tetracyclines.

Body as a whole: Fever, and discoloration of secretions.

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, dyspepsia, stomatitis, glossitis, dysphagia, enamel hypoplasia, enterocolitis, pseudomembranous colitis, pancreatitis, inflammatory lesions (with monilial overgrowth) in the oral and anogenital regions. These reactions have been caused by both the oral and parenteral administration of tetracyclines.

Genitourinary: Vulvovaginitis.

Hepatic toxicity: Hyperbilirubinemia, hepatic cholestasis, increases in liver enzymes, fatal hepatic failure, and jaundice. Hepatitis, including autoimmune hepatitis, and liver failure have been reported (See PRECAUTIONS).

Skin: Alopecia, erythema nodosum, hyperpigmentation of nails, pruritus, toxic epidermal necrolysis, and vasculitis, maculopapular and erythematous rashes. Exfoliative dermatitis has been reported. Fixed drug eruptions have been reported. Lesions occurring on the glans penis have caused balanitis. Erythema multiforme and Stevens-Johnson syndrome have been reported. Photosensitivity is discussed above (See WARNINGS). Pigmentation of the skin and mucous membranes has been reported.

Local Reactions: Injection site erythema and injection site pain.

Respiratory: Cough, dyspnea, bronchospasm, exacerbation of asthma, and pneumonitis.

Renal toxicity: Interstitial nephritis. Elevations in BUN have been reported and are apparently dose related (See WARNINGS). Acute renal failure has been reported.

Musculoskeletal: Arthralgia, arthritis, bone discoloration, myalgia, joint stiffness, and joint swelling.

Hypersensitivity reactions: Urticaria, angioneurotic edema, polyarthralgia, anaphylaxis/anaphylactoid reaction (including shock and fatalities), anaphylactoid purpura, myocarditis, pericarditis, exacerbation of systemic lupus erythematosus, and pulmonary infiltrates with eosinophilia have been reported. A lupus-like syndrome and serum sickness-like reactions also have been reported.

Blood: Agranulocytosis, hemolytic anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, and eosinophilia have been reported.

Central Nervous System: Convulsions, dizziness, hypesthesia, paresthesia, sedation, and vertigo. Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants (See PRECAUTIONS - General). Headache has also been reported.

Other: Thyroid cancer has been reported in the post-marketing setting in association with minocycline products. When minocycline therapy is given over prolonged periods, monitoring for signs of thyroid cancer should be considered. When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. Cases of abnormal thyroid function have been reported.

Tooth discoloration in pediatric patients less than 8 years of age (See WARNINGS) and in adults has been reported.

Oral cavity discoloration (including tongue, lip, and gum) have been reported.

Tinnitus and decreased hearing have been reported in patients on MINOCIN ^® (minocycline for injection).

The following syndromes have been reported. In some cases involving these syndromes, death has been reported. As with other serious adverse reactions, if any of these syndromes are recognized, the drug should be discontinued immediately:

Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present.

Lupus-like syndrome consisting of positive antinuclear antibody; arthralgia, arthritis, joint stiffness, or joint swelling; and one or more of the following: fever, myalgia, hepatitis, rash, and vasculitis.

Serum sickness-like syndrome consisting of fever; urticaria or rash; and arthralgia, arthritis, joint stiffness, or joint swelling. Eosinophilia may be present.

MINOCIN ^® (minocycline) for Injection contains magnesium sulfate heptahydrate (See DESCRIPTION). Adverse effects that may be associated with magnesium intoxication include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and CNS depression proceeding to respiratory paralysis (See PRECAUTIONS).

The adverse events more commonly seen in overdose are dizziness, nausea, and vomiting.

No specific antidote for minocycline is known.

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures. Minocycline is not removed in significant quantities by hemodialysis or peritoneal dialysis.

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

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.

MINOCIN ^® (minocycline) for Injection is supplied as 100 mg single-use vials of sterile lyophilized powder.

NDC 70842-160-01: 100 mg single-use vial

NDC 70842-160-10: units of 10 x 1 single-use 100 mg vials

Store at Controlled Room Temperature 20° to 25°C (68° to 77°F).

Minocycline hydrochloride has been observed to cause a dark discoloration of the thyroid in experimental animals (rats, minipigs, dogs, and monkeys). In the rat, chronic treatment with minocycline hydrochloride has resulted in goiter accompanied by elevated radioactive iodine uptake and evidence of thyroid tumor production. Minocycline hydrochloride has also been found to produce thyroid hyperplasia in rats and dogs.

his product's label may have been updated. For current package insert and further product information, please visit www.minociniv.com or call our toll-free number: 1-844-633-6568. Call between 9:00 a.m. and 5:00 p.m. Eastern Time, Monday through Friday.

Manufactured for Rempex Pharmaceuticals
A wholly‑owned subsidiary of
Melinta Threapeutics, Inc.
All rights reserved.

Marketed and Distributed by
Melinta Threapeutics, Inc.
Lincolnshire, IL 60069

05/19
MEL080-R001

Principal Display Panel
NDC 65293-014-01
Minocin ^®
(minocycline)
for injection
100 mg per vial
Must be reconstituted then diluted.
For Intravenous Infusion.
Sterile Single-use vial -
Discard unused portion.

Minocin (minocycline) for injection 100 mg vial

Principal Display Panel
NDC 65293-014-01
Minocin ^®
(minocycline)
for injection
100 mg per vial
Must be reconstituted then diluted.
For Intravenous Infusion.
Single-use vial -
Discard Unused Portion.

Minocin (minocycline) for injection 100 mg carton