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Thursday, September 29, 2016

Omepril

Omepril may be available in the countries listed below.

Ingredient matches for Omepril

Omeprazole

Omeprazole is reported as an ingredient of Omepril in the following countries:

Ecuador

International Drug Name Search

Wednesday, September 28, 2016

Ofloxacin

Ofloxacin TABLETS 200 mg, 300 mg, and 400 mg

7180

7181

7182

Rx only

Warning

Fluoroquinolones, including Ofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants (see WARNINGS).

Fluoroquinolones, including Ofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid Ofloxacin in patients with known history of myasthenia gravis (see WARNINGS).

Ofloxacin Description

Ofloxacin tablets are a synthetic broad-spectrum antimicrobial agent for oral administration. Chemically, Ofloxacin, a fluorinated carboxyquinolone, is the racemate, (±) - 9 - fluoro - 2,3 - dihydro - 3 - methyl - 10 - (4 - methyl - 1 - piperazinyl) - 7 - oxo - 7H - pyrido[1,2,3 - de] - 1,4 - benzoxazine - 6 - carboxylic acid. The chemical structure is:

C18H20FN3O4 M.W. 361.4

Ofloxacin is an off-white to pale yellow crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine. The relative solubility characteristics of Ofloxacin at room temperature, as defined by USP nomenclature, indicate that Ofloxacin is considered to be soluble in aqueous solutions with pH between 2 and 5. It is sparingly to slightly soluble in aqueous solutions with pH 7 (solubility falls to 4 mg/mL) and freely soluble in aqueous solutions with pH above 9. Ofloxacin has the potential to form stable coordination compounds with many metal ions. This in vitro chelation potential has the following formation order: Fe+3 > Al+3 > Cu+2 > Ni+2 > Pb+2 > Zn+2 > Mg+2 > Ca+2 > Ba+2.

Ofloxacin tablets contain the following inactive ingredients: corn starch, hydroxypropyl cellulose, hypromellose, lactose anhydrous, magnesium stearate, polyethylene glycol 400, polysorbate 80, sodium starch glycolate, and titanium dioxide. Additionally, the 200 mg tablets contain iron oxide yellow and the 400 mg tablets contain iron oxide yellow and iron oxide red.

Ofloxacin - Clinical Pharmacology

Following oral administration, the bioavailability of Ofloxacin in the tablet formulation is approximately 98%. Maximum serum concentrations are achieved one to two hours after an oral dose. Absorption of Ofloxacin after single or multiple doses of 200 to 400 mg is predictable, and the amount of drug absorbed increases proportionately with the dose. Ofloxacin has biphasic elimination. Following multiple oral doses at steady-state administration, the half-lives are approximately 4 to 5 hours and 20 to 25 hours. However, the longer half-life represents less than 5% of the total AUC. Accumulation at steady-state can be estimated using a half-life of 9 hours. The total clearance and volume of distribution are approximately similar after single or multiple doses. Elimination is mainly by renal excretion. The following are mean peak serum concentrations in healthy 70 to 80 kg male volunteers after single oral doses of 200, 300, or 400 mg of Ofloxacin or after multiple oral doses of 400 mg.

Oral Dose	Serum Concentration 2 Hours After Admin. (mcg/mL)	Area Under the Curve (AUC(0-∞)) (mcg•h/mL)
200 mg single dose	1.5	14.1
300 mg single dose	2.4	21.2
400 mg single dose	2.9	31.4
400 mg steady-state	4.6	61.0

Steady-state concentrations were attained after four oral doses, and the area under the curve (AUC) was approximately 40% higher than the AUC after single doses. Therefore, after multiple-dose administration of 200 mg and 300 mg doses, peak serum levels of 2.2 mcg/mL and 3.6 mcg/mL, respectively, are predicted at steady-state.

In vitro, approximately 32% of the drug in plasma is protein bound.

The single dose and steady-state plasma profiles of Ofloxacin injection were comparable in extent of exposure (AUC) to those of Ofloxacin tablets when the injectable and tablet formulations of Ofloxacin were administered in equal doses (mg/mg) to the same group of subjects. The mean steady-state AUC(0-12) attained after the intravenous administration of 400 mg over 60 min was 43.5 mcg•h/mL; the mean steady-state AUC(0-12) attained after the oral administration of 400 mg was 41.2 mcg•h/mL (two one-sided t-test, 90% confidence interval was 103 to 109) (see following chart).

Between 0 and 6 h following the administration of a single 200 mg oral dose of Ofloxacin to 12 healthy volunteers, the average urine Ofloxacin concentration was approximately 220 mcg/mL. Between 12 and 24 hours after administration, the average urine Ofloxacin level was approximately 34 mcg/mL.

Following oral administration of recommended therapeutic doses, Ofloxacin has been detected in blister fluid, cervix, lung tissue, ovary, prostatic fluid, prostatic tissue, skin, and sputum. The mean concentration of Ofloxacin in each of these various body fluids and tissues after one or more doses was 0.8 to 1.5 times the concurrent plasma level. Inadequate data are presently available on the distribution or levels of Ofloxacin in the cerebrospinal fluid or brain tissue.

Ofloxacin has a pyridobenzoxazine ring that appears to decrease the extent of parent compound metabolism. Between 65% and 80% of an administered oral dose of Ofloxacin is excreted unchanged via the kidneys within 48 hours of dosing. Studies indicate that less than 5% of an administered dose is recovered in the urine as the desmethyl or N-oxide metabolites. Four to eight percent of an Ofloxacin dose is excreted in the feces. This indicates a small degree of biliary excretion of Ofloxacin.

The administration of Ofloxacin tablets with food does not affect the Cmax and AUC∞ of the drug, but Tmax is prolonged.

Clearance of Ofloxacin is reduced in patients with impaired renal function (creatinine clearance rate ≤ 50 mL/min), and dosage adjustment is necessary (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

Following oral administration to healthy elderly subjects (65 to 81 years of age), maximum plasma concentrations are usually achieved one to two hours after single and multiple twice-daily doses, indicating that the rate of oral absorption is unaffected by age or gender. Mean peak plasma concentrations in elderly subjects were 9 to 21% higher than those observed in younger subjects. Gender differences in the pharmacokinetic properties of elderly subjects have been observed. Peak plasma concentrations were 114% and 54% higher in elderly females compared to elderly males following single and multiple twice-daily doses. [This interpretation was based on study results collected from two separate studies.] Plasma concentrations increase dose-dependently with the increase in doses after single oral dose and at steady state. No differences were observed in the volume of distribution values between elderly and younger subjects. As in younger subjects, elimination is mainly by renal excretion as unchanged drug in elderly subjects, although less drug is recovered from renal excretion in elderly subjects. Consistent with younger subjects, less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites in the elderly. A longer plasma half-life of approximately 6.4 to 7.4 hours was observed in elderly subjects, compared with 4 to 5 hours for young subjects. Slower elimination of Ofloxacin is observed in elderly subjects as compared with younger subjects which may be attributable to the reduced renal function and renal clearance observed in the elderly subjects. Because Ofloxacin is known to be substantially excreted by the kidney, and elderly patients are more likely to have decreased renal function, dosage adjustment is necessary for elderly patients with impaired renal function as recommended for all patients (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION).

MICROBIOLOGY

Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of Ofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

Ofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Ofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Fluoroquinolones, including Ofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β-lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.

Resistance to Ofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 to 10-11). Although cross-resistance has been observed between Ofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to Ofloxacin.

Ofloxacin 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

Staphylococcus aureus (methicillin-susceptible strains)

Streptococcus pneumoniae (penicillin-susceptible strains)

Streptococcus pyogenes

Aerobic gram-negative microorganisms

Citrobacter (diversus) koseri

Enterobacter aerogenes

Escherichia coli

Haemophilus influenzae

Klebsiella pneumoniae

Neisseria gonorrhoeae

Proteus mirabilis

Pseudomonas aeruginosa

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Ofloxacin.

Other microorganisms

Chlamydia trachomatis

The following in vitro data are available, but their clinical significance is unknown.

Ofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of Ofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.

Aerobic gram-positive microorganisms

Staphylococcus epidermidis (methicillin-susceptible strains)

Staphylococcus saprophyticus

Streptococcus pneumoniae (penicillin-resistant strains)

Aerobic gram-negative microorganisms

Acinetobacter calcoaceticus

Bordetella pertussis

Citrobacter freundii

Enterobacter cloacae

Haemophilus ducreyi

Klebsiella oxytoca

Moraxella catarrhalis

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic microorganisms

Clostridium perfringes

Other microorganisms

Chlamydia pneumoniae

Gardnerella vaginalis

Legionella pneumophila

Mycoplasma hominis

Mycoplasma pneumoniae

Ureaplasma urealyticum

Ofloxacin is not active against Treponema pallidum (see WARNINGS).

Many strains of other streptococcal species, Enterococcus species, and anaerobes are resistant to Ofloxacin.

Susceptibility Tests

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC values). These MIC values provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC values should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of Ofloxacin powder. The MIC values should be interpreted according to the following criteria:

For testing Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa:

MIC (mcg/mL)	Interpretation
≤ 2	Susceptible (S)
4	Intermediate (I)
≥ 8	Resistant (R)

For testing Haemophilus influenzae: a

MIC (mcg/mL)	Interpretation
≤ 2	Susceptible (S)

a This interpretive standard is applicable only to broth microdilution susceptibility tests with Haemophilus influenzae using Haemophilus Test Medium.1

The current absence of data on resistant strains precludes defining any results other than “Susceptible.” Strains yielding MIC results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Neisseria gonorrhoeae:b

MIC (mcg/mL)	Interpretation
≤ 0.25	Susceptible (S)
0.5 to 1	Intermediate (I)
≥ 2	Resistant (R)

b These interpretive standards are applicable only to agar dilution tests using GC agar base and 1% defined growth supplement incubated in 5% CO2.

For testing Streptococcus pneumoniae and Streptococcus pyogenes:c

MIC (mcg/mL)	Interpretation
≤ 2	Susceptible (S)
4	Intermediate (I)
≥ 8	Resistant (R)

c These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard Ofloxacin powder should provide the following MIC values:

Microorganism		MICRange (mcg/mL)
Escherichia coli	ATCC 25922	0.015 to 0.12
Haemophilus influenzae	ATCC 49247d	0.016 to 0.06
Neisseria gonorrhoeae	ATCC 49226e	0.004 to 0.016
Pseudomonas aeruginosa	ATCC 27853	1 to 8
Staphylococcus aureus	ATCC 29213	0.12 to 1
Streptococcus pneumoniae	ATCC 49619f	1 to 4

d This quality control range is applicable only to H. influenzae ATCC 49247 tested by a microdilution procedure using Haemophilus Test Medium (HTM).1

e This quality control range is applicable only to N. gonorrhoeae ATCC 49226 tested by an agar dilution procedure using GC agar base with 1% defined growth supplement incubated in 5% CO2.

f This quality control range is applicable only to S. pneumoniae ATCC 49619 tested by a microdilution procedure using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5 mcg Ofloxacin to test the susceptibility of microorganisms to Ofloxacin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 mcg Ofloxacin disk should be interpreted according to the following criteria:

For testing Enterobacteriaceae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa:

Zone Diameter (mm)	Interpretation
≥ 16	Susceptible (S)
13 to 15	Intermediate (I)
≤ 12	Resistant (R)

For testing Haemophilus influenzae:g

Zone Diameter (mm)	Interpretation
≥ 16	Susceptible (S)

g This zone diameter standard is applicable only to disk diffusion tests with Haemophilusinfluenzae using Haemophilus Test Medium (HTM)2 incubated in 5% CO2.

The current absence of data on resistant strains precludes defining any results other than “Susceptible.” Strains yielding zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.

For testing Neisseria gonorrhoeae:h

Zone Diameter (mm)	Interpretation
≥ 31	Susceptible (S)
25 to 30	Intermediate (I)
≤ 24	Resistant (R)

h These zone diameter standards are applicable only to disk diffusion tests using GC agar base and 1% defined growth supplement incubated in 5% CO2.

For testing Streptococcus pneumoniae and Streptococcus pyogenes:i

Zone Diameter (mm)	Interpretation
≥ 16	Susceptible (S)
13 to 15	Intermediate (I)
≤ 12	Resistant (R)

i These zone diameter standards are applicable only to disk diffusion tests performed using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood and incubated in 5% CO2.

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for Ofloxacin.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5 mcg Ofloxacin disk should provide the following zone diameters in these laboratory quality control strains:

Microorganism		Zone Diameter (mm)
Escherichia coli	ATCC 25922	29 to 33
Haemophilus influenzae	ATCC 49247j	31 to 40
Neisseria gonorrhoeae	ATCC 49226k	43 to 51
Pseudomonas aeruginosa	ATCC 27853	17 to 21
Staphylococcus aureus	ATCC 25923	24 to 28
Streptococcus pneumoniae	ATCC 49619l	16 to 21

j This quality control range is applicable only to H. influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM)2 incubated in 5% CO2.

k This quality control range is applicable only to N. gonorrhoeae ATCC 49226 tested by a disk diffusion procedure using GC agar base with 1% defined growth supplement incubated in 5% CO2.

l This quality control range is applicable only to S. pneumoniae ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood and incubated in 5% CO2.

Indications and Usage for Ofloxacin

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ofloxacin tablets and other antibacterial drugs, Ofloxacin tablets 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.

Ofloxacin tablets are indicated for the treatment of adults with mild to moderate infections (unless otherwise indicated) caused by susceptible strains of the designated microorganisms in the infections listed below. Please see DOSAGE AND ADMINISTRATION for specific recommendations.

Acute bacterial exacerbations of chronic bronchitis due to Haemophilus influenzae or Streptococcus pneumoniae.

Community-acquired pneumonia due to Haemophilus influenzae or Streptococcus pneumoniae.

Uncomplicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, or Proteus mirabilis.

Acute, uncomplicated urethral and cervical gonorrhea due to Neisseria gonorrhoeae (see WARNINGS).

Nongonococcal urethritis and cervicitis due to Chlamydia trachomatis (see WARNINGS).

Mixed infections of the urethra and cervix due to Chlamydia trachomatis and Neisseria gonorrhoeae (see WARNINGS).

Acute pelvic inflammatory disease (including severe infection) due to Chlamydia trachomatis and/or Neisseria gonorrhoeae (see WARNINGS).

NOTE: If anaerobic microorganisms are suspected of contributing to the infection, appropriate therapy for anaerobic pathogens should be administered.

Uncomplicated cystitis due to Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa.

Complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter diversus,* or Pseudomonas aeruginosa.*

Prostatitis due to Escherichia coli.

* = Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients.

Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to Ofloxacin. Therapy with Ofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Ofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

Contraindications

Ofloxacin tablets are contraindicated in persons with a history of hypersensitivity associated with the use of Ofloxacin or any member of the quinolone group of antimicrobial agents.

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including Ofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Ofloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug.

THE SAFETY AND EFFICACY OF Ofloxacin IN PEDIATRIC PATIENTS AND ADOLESCENTS (UNDER THE AGE OF 18 YEARS), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED (see PRECAUTIONS, Pediatric Use, Pregnancy, and Nursing Mothers).

In the immature rat, the oral administration of Ofloxacin at 5 to 16 times the recommended maximum human dose based on mg/kg or 1 to 3 times based on mg/m2 increased the incidence and severity of osteochondrosis. The lesions did not regress after 13 weeks of drug withdrawal. Other quinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species (see ANIMAL PHARMACOLOGY).

Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis have been reported in patients receiving quinolones, including Ofloxacin. Quinolones, including Ofloxacin, may also cause central nervous system stimulation which may lead to: tremors, restlessness/agitation, nervousness/anxiety, lightheadedness, confusion, hallucinations, paranoia and depression, nightmares, insomnia, and rarely suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving Ofloxacin, the drug should be discontinued and appropriate measures instituted. Insomnia may be more common with Ofloxacin than some other products in the quinolone class. As with all quinolones, Ofloxacin should be used with caution in patients with a known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction) (see PRECAUTIONS, General, Information for Patients, Drug Interactions and ADVERSE REACTIONS).

Exacerbation of myasthenia gravis

Fluoroquinolones, including Ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid Ofloxacin in patients with known history of myasthenia gravis (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Postmarketing Adverse Events).

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including Ofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. This drug should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated (see PRECAUTIONS and ADVERSE REACTIONS).

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including Ofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome);

vasculitis; arthralgia; myalgia; serum sickness;

allergic pneumonitis;

interstitial nephritis; acute renal insufficiency or failure;

hepatitis; jaundice; acute hepatic necrosis or failure;

anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS).

Peripheral Neuropathy

Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving quinolones, including Ofloxacin. Ofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation in order to prevent the development of an irreversible condition.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Ofloxacin tablets, 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 antibiotic 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated (see ADVERSE REACTIONS).

Ofloxacin has not been shown to be effective in the treatment of syphilis.

Antimicrobial agents used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with Ofloxacin for gonorrhea should have a follow-up serologic test for syphilis after three months and, if positive, treatment with an appropriate antimicrobial should be instituted.

Precautions

General

Prescribing Ofloxacin tablets in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Adequate hydration of patients receiving Ofloxacin should be maintained to prevent the formation of a highly concentrated urine.

Administer Ofloxacin with caution in the presence of renal or hepatic insufficiency/impairment. In patients with known or suspected renal or hepatic insufficiency/impairment, careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of Ofloxacin may be reduced. In patients with impaired renal function (creatinine clearance ≤ 50 mg/mL), alteration of the dosage regimen is necessary (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of quinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs (see ADVERSEREACTIONS, Postmarketing Adverse Events).

As with other quinolones, Ofloxacin should be used with caution in any patient with a known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction) (see WARNINGS and Drug Interactions).

A possible interaction between oral hypoglycemic drugs (e.g., glyburide/glibenclamide) or with insulin and fluoroquinolone antimicrobial agents have been reported resulting in a potentiation of the hypoglycemic action of these drugs. The mechanism for this interaction is not known. If a hypoglycemic reaction occurs in a patient being treated with Ofloxacin, discontinue Ofloxacin immediately and consult a physician (see Drug Interactions and ADVERSE REACTIONS).

As with any potent drug, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy (see WARNINGS and ADVERSE REACTIONS).

Torsade de Pointes

Some quinolones, including Ofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving quinolones, including Ofloxacin. Ofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents.

Information for Patients

Patients should be advised:

to contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue Ofloxacin treatment. The risk of severe tendon disorders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants;

that fluoroquinolones like Ofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Patients should call their healthcare provider right away if you have any worsening muscle weakness or breathing problems;

that antibacterial drugs including Ofloxacin tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Ofloxacin tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Ofloxacin tablets or other antibacterial drugs in the future;

that peripheral neuropathies have been associated with Ofloxacin use. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, they should discontinue treatment and contact their physicians;

to drink fluids liberally;

that mineral supplements, vitamins with iron or minerals, calcium-, aluminum- or magnesium-based antacids, sucralfate or didanosine, chewable/buffered tablets or the pediatric powder for oral solution should not be taken within the two-hour period before or within the two-hour period after taking Ofloxacin (see Drug Interactions);

that Ofloxacin can be taken without regard to meals;

that Ofloxacin may cause neurologic adverse effects (e.g., dizziness, lightheadedness) and that patients should know how they react to Ofloxacin before they operate an automobile or machinery or engage in activities requiring mental alertness and coordination (see WARNINGS and ADVERSE REACTIONS);

that Ofloxacin may be associated with hypersensitivity reactions, even following the first dose, to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face; tightness of the throat, hoarseness), or any other symptom of an allergic reaction (see WARNINGS and ADVERSE REACTIONS);

that photosensitivity/phototoxicity has been reported in patients receiving quinolone antibiotics. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients need to be outdoors while using quinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician;

that if they are diabetic and are being treated with insulin or an oral hypoglycemic drug, to discontinue Ofloxacin immediately if a hypoglycemic reaction occurs and consult a physician (see PRECAUTIONS, General and Drug Interactions);

that convulsions have been reported in patients taking quinolones, including Ofloxacin, and to notify their physician before taking this drug if there is a history of this condition;

that diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible;

to inform their physician of any personal or family history of QTc prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any class IA (quinidine, procainamide), or class III (amiodarone, sotalol) antiarrhythmic agents. Patients should notify their physicians if they have any symptoms of prolongation of the QTc interval including prolonged heart palpitations or a loss of consciousness.

Tuesday, September 27, 2016

Cardizem LA

Generic Name: diltiazem (dil TYE a zem)

Brand Names: Cardizem, Cardizem CD, Cardizem LA, Cartia XT, Dilacor XR, Dilt-CD, Dilt-XR, Diltia XT, Diltiazem Hydrochloride CD, Diltiazem Hydrochloride SR, Diltiazem Hydrochloride XR, Diltiazem Hydrochloride XT, Diltzac, Taztia XT, Tiazac

What is Cardizem LA (diltiazem)?

Diltiazem is in a group of drugs called calcium channel blockers. It works by relaxing the muscles of your heart and blood vessels.

Diltiazem is used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders.

Diltiazem may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Cardizem LA (diltiazem)?

Do not use this medication if you have certain heart conditions such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker), low blood pressure, or if you have recently had a heart attack.

Before taking diltiazem, tell your doctor if you have kidney disease, liver disease, or congestive heart failure.

Diltiazem may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Do not stop taking this medication without first talking to your doctor. If you stop taking diltiazem suddenly, your condition may become worse.

Diltiazem may be only part of a complete program of treatment that also includes diet, exercise, and other medications. Follow your diet, medication, and exercise routines very closely.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms.

What should I discuss with my healthcare provider before taking Cardizem LA (diltiazem)?

You should not use this medication if you are allergic to diltiazem, or if you have:

certain heart conditions, especially "sick sinus syndrome" or "AV block" (unless you have a pacemaker);

low blood pressure; or

if you have recently had a heart attack.

To make sure you can safely take diltiazem, tell your doctor if you have any of these other conditions:

kidney disease;

liver disease;

congestive heart failure; or

if you are also taking clonidine (Catapres).

FDA pregnancy category C. It is not known whether diltiazem will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Diltiazem can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Cardizem LA (diltiazem)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Your doctor may occasionally change your dose to make sure you get the best results.

Take diltiazem with a full glass of water. Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

If you have trouble swallowing a diltiazem capsule whole, ask your doctor or pharmacist if it is safe for you to open the capsule and sprinkle the medicine into a spoonful of applesauce to make swallowing easier. Swallow this mixture right away without chewing. Do not save the mixture for later use. Discard the empty capsule.

Use diltiazem regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Do not stop taking this medication without first talking to your doctor. If you stop taking diltiazem suddenly, your condition may become worse.

If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.

Diltiazem may be only part of a complete program of treatment that also includes diet, exercise, and other medications. Follow your diet, medication, and exercise routines very closely.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood pressure will need to be checked often. Your liver and kidney function may also need to be tested. Visit your doctor regularly.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of diltiazem can be fatal.

Overdose symptoms may include slow heartbeat, weakness, chest pain, shortness of breath, feeling light-headed, or fainting.

What should I avoid while taking Cardizem LA (diltiazem)?

Diltiazem may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid drinking alcohol while taking diltiazem.

Grapefruit and grapefruit juice may interact with diltiazem and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Avoid exposure to sunlight or tanning beds. Diltiazem can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Cardizem LA (diltiazem) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

a red, blistering skin rash;

swelling in your hands or feet;

trouble breathing;

slow heartbeats;

dizziness, fainting, fast or pounding heartbeat;

upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects may include:

headache;

dizziness, weakness, tired feeling;

upset stomach, nausea;

sore throat, cough, stuffy nose; or

flushing (warmth, redness, or tingly feeling).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Cardizem LA (diltiazem)?

Tell your doctor about all other medicines you use, especially:

amiodarone (Cordarone, Pacerone);

buspirone (BuSpar);

carbamazepine (Carbatrol, Tegretol);

cimetidine (Tagamet);

cyclosporine (Gengraf, Neoral, Sandimmune);

digoxin (digitalis, Lanoxin, Lanoxicaps);

quinidine (Quin-G);

rifampin (Rifadin, Rimactane, Rifater);

an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), or telithromycin (Ketek);

antifungal medication such as itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), miconazole (Oravig), or voriconazole (Vfend);

a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Dutoprol, Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others;

cholesterol medications such as atorvastatin (Lipitor, Caduet), fluvastatin (Lescol), lovastatin (Mevacor, Altoprev, Advicor), pravastatin (Pravachol), rosuvastatin (Crestor), or simvastatin (Zocor, Simcor, Vytorin);

HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), or ritonavir (Norvir, Kaletra); or

a sedative such as midazolam (Versed) or triazolam (Halcion).

This list is not complete and other drugs may interact with diltiazem. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Cardizem LA resources

Cardizem LA Side Effects (in more detail)
Cardizem LA Use in Pregnancy & Breastfeeding
Drug Images
Cardizem LA Drug Interactions
Cardizem LA Support Group
1 Review for Cardizem LA - Add your own review/rating

Cardizem LA 24-Hour Extended-Release Beads Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

Cardizem LA Advanced Consumer (Micromedex) - Includes Dosage Information

Cardizem LA Prescribing Information (FDA)

Diltiazem Prescribing Information (FDA)

Cardizem Prescribing Information (FDA)

Cardizem Consumer Overview

Cardizem MedFacts Consumer Leaflet (Wolters Kluwer)

Cardizem CD Prescribing Information (FDA)

Cardizem CD 24-Hour Sustained-Release Beads Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Cartia XT Prescribing Information (FDA)

DILT-CD Prescribing Information (FDA)

Dilacor XR 24-Hour Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Dilacor XR Prescribing Information (FDA)

Dilt-XR Prescribing Information (FDA)

Diltia XT Prescribing Information (FDA)

Diltiazem Hydrochloride Monograph (AHFS DI)

Matzim LA Prescribing Information (FDA)

Taztia XT Prescribing Information (FDA)

Taztia XT 24-Hour Extended-Release Beads Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Tiazac Prescribing Information (FDA)

Tiazac Consumer Overview

Compare Cardizem LA with other medications

Angina Pectoris Prophylaxis
Atrial Fibrillation
Atrial Flutter
Heart Failure
High Blood Pressure
Raynaud's Syndrome
Supraventricular Tachycardia

Where can I get more information?

Your pharmacist can provide more information about diltiazem.

See also: Cardizem LA side effects (in more detail)

Sumycin

Generic Name: Tetracycline
Class: Tetracyclines
VA Class: AM250
CAS Number: 60-54-8

Introduction

Antibacterial; antibiotic derived from Streptomyces aureofaciens^b ^c ^d or produced semisynthetically from oxytetracycline.^b

Uses for Sumycin

Respiratory Tract Infections

Treatment of respiratory tract infections caused by Mycoplasma pneumoniae.^c ^d ¹⁰⁴

Treatment of respiratory tract infections caused by Haemophilus influenzae, Streptococcus pneumoniae, or Klebsiella.^c ^d ¹⁰⁴ Should only be used for treatment of infections caused by these bacteria when in vitro susceptibility tests indicate the organism is susceptible.^c ^d ^a

Acne

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

Actinomycosis

Treatment of actinomycosis caused by Actinomyces israelii;¹⁰⁴ ¹¹⁴ ^c ^d oral tetracyclines (usually doxycycline or tetracycline) used as follow-up after initial parenteral penicillin G.¹¹⁴

Amebiasis

Adjunct to amebicides for treatment of acute intestinal amebiasis.^c ^d Tetracyclines not included in current recommendations for treatment of amebiasis caused by Entamoeba.¹¹² ¹¹⁴

Anthrax

Alternative to doxycycline for postexposure prophylaxis to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores (inhalational anthrax).¹²² Initial drug of choice for such prophylaxis is ciprofloxacin or doxycycline;¹¹⁴ ¹²² ¹²³ ¹²⁷ doxycycline is the preferred tetracycline because of ease of administration and proven efficacy in monkey studies.¹²²

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 ^d ¹²² ¹²³ 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.¹²² ¹²³ ⁱ

Balantidiasis

Treatment of balantidiasis† caused by Balantidium coli; drug of choice.¹¹² ¹¹⁴

Bartonella Infections

Treatment of bartonellosis caused by Bartonella bacilliformis.^c ^d

Brucellosis

Treatment of brucellosis;¹⁰⁴ ¹¹⁴ ^c ^d tetracyclines (usually doxycycline or tetracycline) considered drugs of choice.¹⁰⁴ ¹¹⁴ Used in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),¹¹⁴ especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).¹¹⁴

Burkholderia Infections

Treatment of glanders† caused by Burkholderia mallei.¹⁰⁴ ^m Experience is limited regarding treatment of human cases; optimum regimens not identified.¹²³ ^m Some clinicians suggest streptomycin used in conjunction with tetracycline or chloramphenicol or imipenem monotherapy.¹⁰⁴ Other clinicians suggest that, pending results of in vitro susceptibility tests, regimens used for treatment of melioidosis can be used for initial empiric treatment of glanders.¹²³ Doxycycline is the preferred tetracycline for treatment of melioidosis caused by susceptible B. pseudomallei.¹²³ ^m

Campylobacter Infections

Treatment of infections caused by Campylobacter.^c ^d Tetracyclines (usually doxycycline) are alternatives,¹¹⁴ not drugs of choice for C. jejuni.¹⁰⁴ ¹¹⁴

Chancroid

Treatment of chancroid caused by Haemophilus ducreyi.^c ^d Not included in CDC recommendations for treatment of chancroid;¹⁰¹ CDC and others recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin.¹⁰¹ ¹⁰²

Chlamydial Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis.^c ^d ¹⁰² 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 ^d ¹⁰⁴ Consider that anti-infectives may not eliminate C. trachomatis in all cases of chronic trachoma.^c ^d

Treatment of lymphogranuloma venereum (genital, inguinal, or anorectal infections) caused by C. trachomatis.^c ^d ¹⁰² ¹⁰⁴ Doxycycline is the preferred tetracycline for these infections.¹⁰¹ ¹¹⁴

Treatment of psittacosis (ornithosis) caused by C. psittaci.¹⁰⁰ ¹⁰⁴ ¹¹⁴ ^c ^d Doxycycline and tetracycline are drugs of choice.¹⁰⁰ ¹¹⁴ For initial treatment of severely ill patients, use IV doxycycline.¹⁰⁰

Clostridium Infections

Alternative for treatment of infections caused by Clostridium.^c ^d Tetracyclines are alternatives to metronidazole or penicillin G for adjunctive treatment of C. tetani infections.¹⁰⁴

Dientamoeba fragilis Infections

Treatment of Dientamoeba fragilis infections.¹¹² Drugs of choice are iodoquinol, paromomycin, tetracycline, or metronidazole.¹¹²

Enterobacteriaceae Infections

Treatment of infections caused by susceptible Escherichia coli, Enterobacter aerogenes, Klebsiella, or Shigella.^c ^d Only use for treatment of infections caused by these common gram-negative bacteria when other appropriate anti-infectives are contraindicated or ineffective^a and when in vitro susceptibility tests indicate the organism is susceptible.^a ^c ^d

Fusobacterium Infections

Alternative to penicillin G for the treatment of infections caused by Fusobacterium fusiforme (Vincent's infection).^c ^d

Gonorrhea and Associated Infections

Alternative for treatment of uncomplicated gonorrhea caused by susceptible Neisseria gonorrhoeae.^c ^d Tetracyclines are considered inadequate therapy and are not recommended by CDC for treatment of gonorrhea.¹⁰¹ ^a

Empiric treatment of epididymitis most likely caused by N. gonorrhoeae or C. trachomatis; used in conjunction with IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

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

Helicobacter pylori Infection and Duodenal Ulcer Disease

Treatment of Helicobacter pylori infection and duodenal ulcer (active or a history of duodenal ulcer);¹⁰⁴ ^e eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.¹⁰⁴ ^e

Used in a multiple-drug regimen that includes tetracycline, metronidazole, and bismuth subsalicylate and a histamine H₂-receptor antagonist.^e If initial 14-day regimen does not eradicate H. pylori, a retreatment regimen that does not include metronidazole should be used.^e

Leptospirosis

Tetracyclines are alternatives to penicillin G for treatment of leptosporosis†.¹⁰⁴ Doxycycline is the preferred tetracycline for treatment or prevention of these infections.^l

Listeria Infections

Alternative for treatment of listeriosis caused by Listeria monocytogenes.^c ^d Not usually considered a drug of choice or alternative for these infections.¹⁰⁴ ¹¹⁴

Malaria

Treatment of uncomplicated malaria† caused by chloroquine-resistant Plasmodium falciparum or chloroquine-resistant P. vivax and when the plasmodial species has not been identified.¹¹² ¹²⁹

CDC and others state treatments of choice for uncomplicated chloroquine-resistant P. falciparum malaria are a regimen of oral quinine in conjunction with oral doxycycline, tetracycline, or clindamycin or a regimen of atovaquone and proguanil.¹¹² ¹²⁹ A regimen of quinine and doxycycline (or tetracycline) generally preferred over quinine and clindamycin,¹²⁹ except for young children or pregnant women who should not receive tetracyclines.¹²⁹ Quinine in conjunction with tetracycline (or doxycycline) also a regimen of choice for chloroquine-resistant P. vivax malaria.¹¹² ¹²⁹

Treatment of severe malaria caused by P. falciparum†;¹¹² ¹²⁹ used in conjunction with IV quinidine gluconate initially and then oral quinine when an oral regimen is tolerated.¹¹² ¹²⁹

Active only against asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. vivax malaria or provide a radical cure; primaquine usually also is indicated to eradicate hypnozoites and prevent relapse in patients treated for P. vivax malaria.¹¹² ¹²⁹

Assistance with diagnosis or treatment of malaria available from the CDC Malaria Epidemiology Branch by contacting the CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.¹²⁹

Nocardiosis

Tetracyclines are alternatives to co-trimoxazole for treatment of nocardiosis† caused by Nocardia.¹⁰⁴ ¹¹⁴

Nongonococcal Urethritis

Treatment of nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum, C. trachomatis, or Mycoplasma.^c ^d ¹⁰⁴ Doxycycline usually is the tetracycline of choice for NGU.¹⁰¹ ¹⁰²

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

Pasteurella multocida Infections

Treatment of infections caused by Pasteurella multocida†.¹⁰⁴ ¹¹⁴ Tetracyclines (usually doxycycline) are alternatives to penicillin G.¹⁰⁴ ¹¹⁴

Plague

Treatment of plague caused by Yersinia pestis,^c ^d ¹⁰⁴ ¹¹⁴ ¹²⁴ including naturally occurring or endemic bubonic, septicemic, or pneumonic plague and plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism.¹²⁴ Regimen of choice is streptomycin or gentamicin;¹⁰⁴ ¹¹⁴ ¹²³ ¹²⁴ alternatives are doxycycline, tetracycline, ciprofloxacin, or chloramphenicol.¹²³ ¹²⁴ For plague meningitis, some experts recommend that chloramphenicol be included in the treatment regimen.¹²³

Postexposure prophylaxis following a high-risk exposure to Y. pestis† (e.g., household, hospital, or other close contact with an individual who has pneumonic plague; laboratory exposure to viable Y. pestis; confirmed exposure in the context of biologic warfare or bioterrorism).¹²³ ¹²⁴ Doxycycline may be drug of choice;¹¹⁴ ¹²³ ¹²⁴ alternatives are tetracycline, ciprofloxacin, or chloramphenicol.¹²³ Prophylaxis not required for asymptomatic contacts of individuals with bubonic plague, but observe such contacts for 1 week and initiate treatment if symptoms occur.¹²³

Rat-bite Fever

Treatment of rat-bite fever† caused by Streptobacillus moniliformis or Spirillum minus.¹⁰⁴ ¹¹⁴ Tetracyclines (usually doxycycline) are alternatives to penicillin G.¹⁰⁴ ¹¹⁴

Relapsing Fever

Treatment of relapsing fever caused by Borrelia recurrentis.¹⁰⁴ ^c ^d Tetracyclines are drugs of choice.¹⁰⁴

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.¹¹⁴ ¹²³ ^c ^d Doxycycline is the drug of choice for most rickettsial infections.¹¹⁴ ^a ^j

Syphilis

Alternative to penicillin G for treatment of primary, secondary, latent, or tertiary syphilis (not neurosyphilis) in nonpregnant adults and adolescents hypersensitive to penicillins.¹⁰¹ ¹¹⁴ ^c ^d 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, including naturally occurring or endemic tularemia and tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.¹⁰⁴ ¹¹⁴ ¹²³ ^c ^d ^f Drugs of choice are streptomycin or gentamicin; alternatives are tetracyclines (usually doxycycline), ciprofloxacin, or chloramphenicol.¹⁰⁴ ¹¹⁴ ^f Risk of relapse and primary treatment failure may be higher with the alternatives.^f

Postexposure prophylaxis of tularemia† following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism.¹²³ ^f Drugs of choice are doxycycline, tetracycline, or ciprofloxacin.¹²³ ^f Postexposure prophylaxis usually not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.^f

Vibrio Infections

Treatment of cholera caused by Vibrio cholerae.¹⁰⁴ ¹¹⁴ ^c ^d ^h Doxycycline and tetracycline are drugs of choice; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.¹⁰⁴ ¹¹⁴ ^c ^d ^h

Treatment of severe V. parahaemolyticus† infection when anti-infective therapy is indicated in addition to supportive care.^h

Treatment of infections caused by V. vulnificus†.¹⁰⁴ Optimum anti-infective therapy has not been identified; a tetracycline or third generation cephalosporin (e.g., cefotaxime, ceftazidime) is recommended.¹⁰⁴ ^g ^h Because the case fatality rate associated with V. vulnificus is high, initiate anti-infective therapy promptly if indicated.^g

Yaws

Alternative to penicillin G for treatment of yaws caused by Treponema pertenue.¹⁰⁴ ^c ^d

Yersinia Infections

Treatment of plague or postexposure prophylaxis of plague†.^c ^d ¹⁰⁴ ¹¹⁴ ¹²³ ¹²⁴ (See Plague in Uses.)

Treatment of GI infections caused by Yersinia enterocolitica† or Y. pseudotuberculosis†.¹¹⁴ These GI infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections or when septicemia or other invasive disease occurs.¹¹⁴ Some clinicians suggest the role of oral anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.¹¹⁴

Sumycin Dosage and Administration

Administration

Oral Administration

Administer orally.^c ^d

Administer capsules and tablets with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.^c ^d

Dosage

Available as tetracycline^d and tetracycline hydrochloride;^c dosage expressed in terms of tetracycline hydrochloride.^c ^d

Pediatric Patients

General Pediatric Dosage

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses.^c

Balantidiasis†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.¹¹² ¹¹⁴

Brucellosis

Oral

Children ≥8 years of age: 30–40 mg/kg daily (up to 2 g) in 4 divided doses.¹¹⁴ Duration of treatment usually is 4–6 weeks; more prolonged treatment may be necessary for severe infections or when there are complications.¹¹⁴

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.¹¹⁴ ^c ^d Rifampin can be administered concomitantly (with or without an aminoglycoside) to decrease the risk of relapse.¹¹⁴

Dientamoeba fragilis Infection†

Oral

Children ≥8 years of age: 40 mg/kg daily (up to 2 g) in 4 divided doses given for 10 days.¹¹²

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹¹² ¹²⁹

Treatment of Uncomplicated P. vivax Malaria†

Oral

In addition, a 14-day regimen of oral primaquine (0.6 mg/kg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: 6.25 mg/kg 4 times daily given for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment of Pneumonic Plague

Oral

Children >8 years of age: 25–50 mg/kg daily in 4 divided doses^b given for ≥10–14 days.¹²³ ¹²⁴

Prompt initiation of treatment (within 18–24 hours of symptom onset) is essential.¹²³ ¹²⁴ A parenteral regimen (e.g., IM streptomycin, IM or IV gentamicin, IV doxycycline) is preferred for initial treatment; an oral regimen may be substituted when the patient's condition improves or if a parenteral regimen is unavailable.¹²³ ¹²⁴

Postexposure Prophylaxis following High-risk Exposure†

Oral

Children >8 years of age: 25–50 mg/kg daily in 2 or 4 equally divided doses.^b

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days¹²³ ¹²⁴ or the duration of exposure risk plus 7 days.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days.¹⁰¹ ¹⁰² ¹¹⁴

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

Children >8 years of age: 500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.¹⁰¹ ¹⁰² ¹¹⁴

Vibrio Infections

Cholera

Oral

Children >8 years of age: 50 mg/kg daily in 4 divided doses given for 3 days.¹¹⁴

Adults

General Adult Dosage

Oral

1–2 g daily in 2–4 divided doses.^c ^d

500 mg twice daily or 250 mg 4 times daily may be adequate for mild to moderate infections; severe infections may required 500 mg 4 times daily.^c ^d

Respiratory Tract Infections

Mycoplasma pneumoniae Infections

Oral

1–2 g daily in 2–4 equally divided doses.^b Duration of treatment usually is 1–4 weeks.^b

Acne

Oral

1 g daily given in divided doses; when improvement occurs in 1–2 weeks, decrease slowly to a maintenance dosage of 125–500 mg daily.^b ^c ^d Continue maintenance dosage until clinical improvement allows discontinuation of the drug.^b

Actinomycosis

Oral

1–2 g daily for 6–12 months as follow-up to penicillin G.^b

Anthrax

Postexposure Prophylaxis following Exposure in the Context of Biologic Warfare or Bioterrorism

Oral

500 mg every 6 hours given for ≥60 days.¹²²

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,¹²³ ^k but prolonged postexposure prophylaxis usually required.¹²² ¹²³ A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure.^k CDC recommends that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) be continued for 60 days.¹²² ¹²³ The US Working Group on Civilian Biodefense and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.¹²³

Treatment of Inhalational Anthrax

Oral

500 mg every 6 hours.¹²²

Initial parenteral regimen preferred; use oral regimen for initial treatment only 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).¹²² ⁱ Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.¹⁰² ¹²³ ⁱ

Balantidiasis†

Oral

500 mg 4 times daily given for 10 days.¹¹²

Brucellosis

Oral

500 mg 4 times daily given for 3 weeks.^c ^d

If infection is severe or if endocarditis, meningitis, or osteomyelitis are present, administer IM streptomycin or gentamicin during the first 7–14 days of tetracycline therapy.¹¹⁴ ^c ^d Rifampin can be administered concomitantly to decrease the risk of relapse (with or without an aminoglycoside).¹¹⁴

Burkholderia Infections†

Melioidosis†

Oral

2–3 g daily given for 1–3 months.^b In severe cases, some clinicians recommend concomitant chloramphenicol during the first month.^b In patients with extrapulmonary suppurative lesions, continue tetracycline therapy for 6–12 months.^b

Campylobacter Infections

Campylobacter fetus Infections

Oral

1–2 g daily given for 10 days.^b

Chancroid

Oral

1–2 g daily given for 2–4 weeks.^b

Chlamydial Infections

Uncomplicated Urethral, Endocervical, or Rectal Infections

Oral

500 mg 4 times daily given for ≥7 days.¹⁰² ^c ^d

Psittacosis (Ornithosis)

Oral

500 mg 4 times daily given for ≥10–14 days after defervescence.¹⁰⁰

Dientamoeba fragilis Infection†

Oral

500 mg 4 times daily for 10 days.¹¹²

Gonorrhea and Associated Infections

Uncomplicated Gonorrhea

Oral

500 mg 4 times daily given for 7 days.^c ^d No longer recommended for gonorrhea by CDC or other experts.¹⁰¹ ¹⁰²

Empiric Treatment of Epididymitis†

Oral

500 mg 4 times daily given for 10 days; as follow-up to a single dose of IM ceftriaxone.¹⁰²

Granuloma Inguinale (Donovanosis)

Oral

1–2 g daily given for 2–4 weeks.^b

Helicobacter pylori Infection and Duodenal Ulcer Disease

Oral

500 mg in conjunction with metronidazole (250 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with usual dosage of an H₂-receptor antagonist.¹¹⁰

Leptospirosis†

Oral

1–2 g daily given for 5–7 days.^b

Malaria†

Treatment of Uncomplicated Chloroquine-resistant P. falciparum Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹¹² ¹²⁹

Treatment of Uncomplicated P. vivax Malaria†

Oral

250 mg 4 times daily given for 7 days; used in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).¹²⁹

In addition, a 14-day regimen of oral primaquine (30 mg once daily) also may be indicated to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.¹²⁹

Treatment of Severe P. falciparum Malaria†

Oral

250 mg 4 times daily for 7 days; used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) given for a total duration of 3–7 days.¹²⁹ If an IV tetracycline is necessary initially, use IV doxycycline until oral therapy can be tolerated.¹²⁹

Plague

Treatment

Oral

2–4 g daily in 4 divided doses^b given for ≥10–14 days.^b ¹²³

Postexposure Prophylaxis following High-risk Exposure†

Oral

1–2 g daily in 2 or 4 divided doses.¹²³

Duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days¹²³ ¹²⁴ or the duration of exposure risk plus 7 days.¹²³

Relapsing Fever

Oral

1–2 g daily until afebrile for 7 days.^b A single 500-mg dose may be effective in some patients.^b

Rickettsial Infections

Oral

1–2 g daily in 2–4 divided doses.^b Duration of treatment usually is ≥3–7 days or until patients has been afebrile for approximately 2–3 days.^b

Q Fever

Oral

500 mg every 6 hours given for ≥14 days for treatment of acute Q fever.¹²³

For prophylaxis against Q fever†, 500 mg every 6 hours given for ≥5–7 days may prevent clinical disease if initiated 8–12 days after exposure; such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1–7 days) after exposure.¹²³

Syphilis

Primary or Secondary Syphilis

Oral

500 mg 4 times daily given for 14 days recommended by CDC and others.¹⁰¹ ¹⁰² Manufacturer recommends a total dosage of 30–40 g in equally divided doses given over 10–15 days.^c ^d

Latent Syphilis or Tertiary Syphilis (Except Neurosyphilis)

Oral

500 mg 4 times daily given for 14 days for early latent syphilis (duration <1 year) or 500 mg 4 times daily given for 28 days for late latent syphilis (duration≥1 year), latent syphilis of unknown duration, or tertiary syphilis.¹⁰¹ ¹⁰²

Tularemia

Treatment

Oral

500 mg 4 times daily¹²³ given for ≥14–21 days.¹²³ ^f Relapse may occur as long as 6 months after treatment with tetracycline; however, retreatment with the same dosage usually is curative.^b

Postexposure Prophylaxis following High-risk Exposure†

Oral

500 mg 4 times daily.¹²³

Initiate postexposure prophylaxis within 24 hours of exposure and continue for ≥14 days.¹²³ ^f

Vibrio Infections

Cholera

Oral

1–2 g daily given for 2–3 days.^b 500 mg 4 times daily for 3 days also has been recommended.¹⁰³

Yaws

Oral

1–2 g daily given for 10–14 days.^b

Prescribing Limits

Pediatric Patients

Malaria

Treatment of Severe P. falciparum Malaria†

Oral

Children ≥8 years of age: Maximum 1g daily.¹²⁹

Special Populations

Renal Impairment

Adjust dosage by decreasing doses or increasing dosing interval.^c ^d

Cautions for Sumycin

Contraindications

Known hypersensitivity to any tetracycline.^c ^d

Helidac Therapy (kit containing tetracycline, metronidazole, bismuth subsalicylate) contraindicated in pregnant or nursing women, pediatric patients, patients with hepatic or renal impairment, patients with known allergy to aspirin or salicylates, and those with known hypersensitivity to any component of the kit.^e

Warnings/Precautions

Warnings

Dental and Bone Effects

Use during tooth development (e.g., pregnancy, children <8 years of age) may cause permanent yellow-gray to brown discoloration of teeth and enamel hypoplasia.^c ^d Effects are most common following long-term use, but may occur following repeated short-term use.^c ^d

Tetracyclines form a stable calcium complex in any bone-forming tissue.^c ^d Reversible decrease in fibula growth rate has occurred in young animals receiving oral tetracycline.^c ^d

Use not recommended in children <8 years of age unless other appropriate drugs are ineffective or are contraindicated or unless the benefits in certain indications (e.g., anthrax) outweigh the risks.¹¹⁴ ^c ^d (See Pediatric Use under Cautions.)

Fetal/Neonatal Morbidity

Animal studies indicate possible fetal toxicity (e.g., retardation of skeletal development) and embryotoxicity.^c ^d If used during pregnancy or if patient becomes pregnant while receiving tetracycline, patient should be apprised of the potential hazard to the fetus.^c ^d (See Pregnancy under Cautions.)

Renal Effects

Tetracyclines have antianabolic effects and may increase BUN.^c ^d

In patients with impaired renal function, high serum tetracycline concentrations may result in azotemia, hyperphosphatemia, and acidosis.^c ^d Excessive drug accumulation and possible liver toxicity may occur if usual dosage is used patients with renal impairment.^c ^d (See Renal Impairment under Dosage and Administration.)

Do not use tetracycline preparations past their expiration dates.^c ^d Outdated tetracycline preparations are highly nephrotoxic and have, on occasion, produced a Fanconi-like syndrome.^c ^d

Laboratory Monitoring

Periodically assess organ system function, including renal, hepatic and hematopoietic, during long-term therapy.^c ^d

Helidac Therapy

When the kit containing tetracycline, metronidazole, and bismuth subsalicylate (Helidac Therapy) is used for the treatment of H. pylori infection and duodenal ulcer disease, the cautions, precautions, and contraindications associated with metronidazole and bismuth subsalicylate must be considered in addition to those associated with tetracycline.^e

Sensitivity Reactions

Photosensitivity Reactions

Photosensitivity, manifested by an exaggerated sunburn reaction, reported with tetracyclines.^c ^d

Photosensitivity reactions may develop within a few minutes to several hours after sun exposure and usually persist 1–2 days after discontinuance of the drug.^a Most reactions result from accumulation of tetracyclines in skin and are phototoxic in nature; photoallergic reactions may also occur.^a

Discontinue drug at first evidence of skin erythema.^c ^d

Hypersensitivity Reactions

Oral suspension contains sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.^d

Cross-sensitization occurs among the various tetracyclines.^c ^d

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.^c ^d Discontinue drug and institute appropriate therapy if superinfection occurs.^c ^d

Nervous System Effects

Possibility of bulging fontanels in infants and benign intracranial hypertension (pseudotumor cerebri) in adults.^c ^d Effects usually resolve when drug discontinued, but possibility for permanent sequelae exists.^c ^d

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tetracycline and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^c ^d

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^c ^d In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^c ^d

Because many strains of Acinetobacter, Bacteroides, Enterobacter, E. coli, Klebsiella, Shigella, S. pyogenes (group A β-hemolytic streptococci), S. pneumoniae, enterococci, and α-hemolytic streptococci are resistant to tetracycline, in vitro susceptibility tests should be performed if the drug is used for treatment of infections caused by these bacteria.^c ^d

Incision and drainage or other surgical procedures should be performed in conjunction with tetracycline therapy when indicated.^c ^d

Specific Populations

Pregnancy

Category D.^c ^d (See Fetal/Neonatal Morbidity under Cautions.)

Should not be used in pregnant women unless, in the judgement of the clinician, it is essential for the welfare of the patient and benefits outweigh the risks.^c ^d

CDC and others state tetracyclines can be used when necessary for treatment of inhalational anthrax in pregnant women.¹²² ⁱ Since adverse effects on developing teeth and bones are dose-related, CDC suggests the drug might be used for a short period (7–14 days) before 6 months of gestation;ⁱ some clinicians recommend periodic liver function testing if used in pregnant women.¹²²

Malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death)¹