Demeclocycline hydrochloride

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Demeclocycline hydrochloride
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gloria Picoy [2]

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Overview

Demeclocycline hydrochloride is a tetracycline that is FDA approved for the treatment of various types of bacterial infections. Common adverse reactions include photosensitivity.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Demeclocycline hydrochloride dosage is 150 mg oral, every 6 hours or 300 mg oral, every 12 hours. It is indicated for:


Demeclocycline hydrochloride is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:


Demeclocycline hydrochloride is indicated for treatment of infections caused by the following gram-positive microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:


When penicillin is contraindicated, tetracyclines, including demeclocycline hydrochloride, are alternative drugs in the treatment of the following infections:

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Demeclocycline hydrochloride in adult patients.

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Demeclocycline hydrochloride dosage is indicated for:


Demeclocycline hydrochloride is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:


Demeclocycline hydrochloride is indicated for treatment of infections caused by the following gram-positive microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:


When penicillin is contraindicated, tetracyclines, including demeclocycline hydrochloride, are alternative drugs in the treatment of the following infections:


Dosage for Pediatric Patients Above Eight Years of Age
  • Usual daily dose, 7 to 13 mg per kg body weight per day, depending upon the severity of the disease, divided into two to four doses not to exceed adult dosage of 600 mg per day.
  • Gonorrhea patients sensitive to penicillin may be treated with demeclocycline administered as an initial oral dose of 600 mg followed by 300 mg every 12 hours for four days to a total of 3 grams.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Demeclocycline hydrochloride in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Demeclocycline hydrochloride in pediatric patients.

Contraindications

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

Warnings

  • DEMECLOCYCLINE HYDROCHLORIDE, LIKE OTHER TETRACYCLINE-CLASS ANTIBIOTICS, 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.
  • All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in 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 also been noted in animals treated early in pregnancy. 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.
  • Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Phototoxic reactions can occur in individuals taking demeclocycline, and are characterized by severe burns or exposed surfaces resulting from direct exposure of patients to sunlight during therapy with moderate or large doses of demeclocycline. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur, and treatment should be discontinued at the first evidence of erythema of the skin.
  • Administration of demeclocycline hydrochloride has resulted in appearance of the diabetes insipidus syndrome (polyuria, polydipsia and weakness) in some patients on long-term therapy. The syndrome has been shown to be nephrogenic, dose-dependent and reversible on discontinuance of therapy. Patients who are experiencing central nervous system symptoms associated with demeclocycline therapy should be cautioned about driving vehicles or using hazardous machinery while on demeclocycline therapy.


Clostridium difficile associated with diarrhea (CDAD)
  • Clostridium difficile associated with diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including demeclocycline hydrochloride, 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.

Adverse Reactions

Clinical Trials Experience

Gastrointestinal
  • Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, pancreatitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, increases in liver enzymes, and hepatic toxicity has been reported rarely.
  • Rarely, hepatitis and liver failure have been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines.
  • Instances of esophageal ulcerations have been reported in patients receiving oral tetracyclines. Most of the patients were reported to have taken the medication immediately before lying down.
Skin
Renal toxicity
Hypersensitivity reactions
Hematologic
CNS
Other
  • When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur. Very rare cases of abnormal thyroid function have been reported.
  • Tooth discoloration has occurred in pediatric patients less than 8 years of age, and also has been reported rarely in adults.

Postmarketing Experience

There is limited information regarding Demeclocycline hydrochloride Postmarketing Experience in the drug label.

Drug Interactions

  • Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. Since bacteriostatic drugs may interfere with the bactericidal action of penicillins, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.
  • Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective.
  • The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.

´* Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium, and by iron-containing preparations.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): D 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.
Pregnancy Category (AUS): D There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Demeclocycline hydrochloride in women who are pregnant.

Labor and Delivery

The effect of tetracyclines on labor and delivery is unknown.

Nursing Mothers

Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from the tetracyclines, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Not for use in patients younger than eight years of age.

Geriatic Use

There is no FDA guidance on the use of Demeclocycline hydrochloride in geriatric settings.

Gender

There is no FDA guidance on the use of Demeclocycline hydrochloride with respect to specific gender populations.

Race

There is no FDA guidance on the use of Demeclocycline hydrochloride with respect to specific racial populations.

Renal Impairment

If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated and, if therapy is prolonged, serum level determinations of the drug may be advisable.

Hepatic Impairment

There is no FDA guidance on the use of Demeclocycline hydrochloride in patients with hepatic impairment.

Females of Reproductive Potential and Males

Demeclocycline hydrochloride had no effect on fertility when administered in the diet to male and female rats at a daily intake of 45 times the human dose.

Immunocompromised Patients

There is no FDA guidance one the use of Demeclocycline hydrochloride in patients who are immunocompromised.

Administration and Monitoring

Administration

Oral

Monitoring

There is limited information regarding Demeclocycline hydrochloride Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Demeclocycline hydrochloride and IV administrations.

Overdosage

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

Pharmacology

Demeclocycline hydrochloride structure.png
Demeclocycline hydrochloride
Systematic (IUPAC) name
(2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione
Identifiers
CAS number 127-33-3

64-73-3 (HCl)
ATC code D06AA01 J01AA01 (WHO)
PubChem 5311063
DrugBank DB00618
Chemical data
Formula C21H21ClN2O8 
Mol. mass 464.853 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 60–80%
Protein binding 41–50%
Metabolism Hepatic
Half life 10–17 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D(US)

Legal status

Prescription only

Routes Oral

Mechanism of Action

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

Structure

Chemically it is 7-Chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12, 12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride. The structural formula is:

Demeclocycline hydrochloride chemical structure.png

Pharmacodynamics

There is limited information regarding Demeclocycline hydrochloride Pharmacodynamics in the drug label.

Pharmacokinetics

The absorption of demeclocycline is slower than that of tetracycline. The time to reach the peak concentration is about 4 hours. After a 150 mg oral dose of demeclocycline tablet, the mean concentrations at 1 hour and 3 hours are 0.46 and 1.22 mcg/mL (n = 6), respectively. The serum half-life ranges between 10 and 16 hours. When demeclocycline hydrochloride is given concomitantly with some dairy products, or antacids containing aluminum, calcium, or magnesium, the extent of absorption is reduced by more than 50%. Demeclocycline hydrochloride penetrates well into various body fluids and tissues. The percent of demeclocycline hydrochloride bound to plasma protein is about 40% using a dialysis equilibrium method and 90% using an ultra-filtration method. Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. The rate of demeclocycline hydrochloride renal clearance (35 mL/min/1.73 m2) is less than half that of tetracycline. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.

Nonclinical Toxicology

Mechanism(s) of Resistance
  • Resistance to tetracyclines may be mediated by efflux, alteration in the target site of tetracycline, enzymatic inactivation, and decreased bacterial permeability to the tetracycline or a combination of these mechanisms.
  • Cross-resistance between antibiotics of the tetracycline family occurs.
Carcinogenesis and Mutagenesis
  • Long-term studies in animals to evaluate carcinogenic potential of demeclocycline hydrochloride have not been conducted.
  • However, there has been evidence of oncogenic activity in rats in studies with the related antibiotics oxytetracycline (adrenal and pituitary tumors) and minocycline (thyroid tumors).
  • Although mutagenicity studies of demeclocycline hydrochloride have not been conducted, positive results in in vitro mammalian cell assays (i.e., mouse lymphoma and Chinese hamster lung cells) have been reported for related antibiotics (tetracycline hydrochloride and oxytetracycline).

Clinical Studies

There is limited information regarding Demeclocycline hydrochloride Clinical Studies in the drug label.

How Supplied

Demeclocycline Hydrochloride Tablets 150 mg

  • Packaged in bottle of 100 tablets

Demeclocycline Hydrochloride Tablets 300 mg

  • Packaged in bottle of 48 tablets

Storage

Store at 20º to 25ºC (68º to 77ºF)

Images

Drug Images

Package and Label Display Panel

Demeclocycline hydrochloride 150 mg FDA package label.png
Demeclocycline hydrochloride 300 mg FDA package label.png
Demeclocycline hydrochloride 150 mg.png
This image of the FDA label is provided by the National Library of Medicine.
Demeclocycline hydrochloride 300 mg.png
This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema. Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective. Patients should be informed that demeclocycline hydrochloride tablets should be taken at least 1 hour before meals or 2 hours after meals. Unused supplies of tetracycline antibiotics should be discarded by the expiration date. Patients who are experiencing headache, dizziness, light-headedness, vertigo, or blurred vision while on demeclocycline therapy, should be cautioned about driving vehicles or using hazardous machinery while receiving demeclocycline therapy.

Patients should be counseled that antibacterial drugs, including demeclocycline hydrochloride tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When demeclocycline hydrochloride 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:

  • decrease the effectiveness of the immediate treatment and
  • increase the likelihood that bacteria will develop resistance and will not be treatable by demeclocycline hydrochloride tablets or other antibacterial drugs in the future.

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.

Precautions with Alcohol

Alcohol-Demeclocycline hydrochloride interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

There is limited information regarding Demeclocycline hydrochloride Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. "FDA LABEL: DEMECLOCYCLINE HYDROCHLORIDE- demeclocycline hydrochloride tablet, film coated".





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