Demeclocycline (Declomycin) - Class, Uses, Brands, MOA

Demeclocycline (Declomycin) is a tetracycline antibiotic that is used to treat susceptible infections. It is also used in the treatment of SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Indications of Demeclocycline (Declomycin):

Note: Alternative tetracycline agents (eg, doxycycline, minocycline, tetracycline) are generally preferred over demeclocycline as an antibiotic.

Acne:
- It is indicated as adjunctive therapy in severe acne.
Actinomycosis:
- It is given for the treatment of actinomycosis caused by Actinomyces israelii when penicillin is contraindicated.
Acute intestinal amebiasis:
- It is given as adjunct therapy to amoebicides in acute intestinal amoebiasis.
Anthrax:
- When penicillin is contraindicated, it is given for the treatment of anthrax due to Bacillus anthracis.
Cholera:
- It is effective in the treatment of cholera caused by Vibrio cholerae.
Clostridium:
- When penicillin is contraindicated, it is used for the management of clostridial disease caused by Clostridium spp.
Gram-negative infections:
- It is indicated for the treatment of infections caused by Escherichia coli, Enterobacter aerogenes, Shigella species, and Acinetobacter species.
Listeriosis:
- When penicillin is contraindicated, it is used for the management of listeriosis due to Listeria monocytogenes.
Ophthalmic infections:
- Treatment of inclusion conjunctivitis or trachoma caused by Chlamydia trachomatis can be done by demeclocycline.
Plague:
- It is effective in the treatment of plague due to Yersinia pestis.
Relapsing fever:
- Relapsing fever caused by Borrelia recurrentis can be treated by demeclocycline.
Respiratory tract infections:
- It is effective in the treatment of respiratory tract infections caused by Haemophilus influenzae, Klebsiella species, or Mycoplasma pneumoniae, upper respiratory tract infections caused by Streptococcus pneumoniae.
Rickettsial infections:
- It is used for treating Rocky Mountain spotted fever, typhus fever, and the typhus group, Q fever, rickettsialpox and tick fevers caused by Rickettsiae.
Sexually transmitted diseases:
- Treatment of:
  - lymphogranuloma venereum caused by Chlamydia trachomatis;
  - granuloma inguinale caused by Klebsiella granulomatis;
  - chancroid caused by Haemophilus ducreyi;
  - nongonococcal urethritis caused by Ureaplasma urealyticum or Chlamydia trachomatis;
  - when penicillin is contraindicated, uncomplicated urethritis in men caused by Neisseria gonorrhea and other uncomplicated gonococcal infections, infections in women caused by N. gonorrhoea and
  - syphilis caused by Treponema pallidum subspecies pallidum.
- Demeclocycline is not a recommended alternative for gonorrhea according to the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases guidelines. Consult current guidelines for recommendations.
Skin and skin structure infections:
- Treatment of skin and skin structure infections caused by Staphylococcus aureus can be treated by demeclocycline.
Urinary tract infections:
- It is effective in the management of infections of the urinary tract caused by Klebsiella species.
Vincent infection:
- When penicillin is contraindicated, it is given for the treatment of Vincent infection caused by Fusobacterium fusiforme.
Yaws:
- When penicillin is contraindicated, it is used for treating yaws caused by Treponema pallidum subspecies pertenue.
Zoonotic infections:
- Treatment of:
  - Psittacosis (ornithosis) caused by Chlamydophila psittaci;
  - Tularemia caused by Francisella tularensis;
  - Brucellosis caused by Brucella species (in conjunction with streptomycin);
  - Bartonellosis caused by Bartonella bacilliformis;
  - Infections caused by Campylobacter fetus.
Off Label Use of Demeclocycline in Adults:
- Chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Demeclocycline dose in Adults

Demeclocycline dose in the treatment of Susceptible infections:

Oral: 150 mg 4 times daily or 300 mg twice daily.

Demeclocycline (Declomycin) dose in the treatment of SIADH (off-label):

Oral: 600 to 1,200 mg/day.

Note:

Limited high-quality evidence exists to define the clinical role, if any, of demeclocycline in this condition.
Demeclocycline use for the management of hyponatremia in patients with SIADH is not recommended by European clinical practice guidelines.

Demeclocycline dose in Childrens

Demeclocycline dose in the treatment of Susceptible infections in children:

Note: Alternative tetracyclines are recommended (eg, doxycycline, minocycline, tetracycline) over demeclocycline as an antibacterial agent.

Children ≥8 years and Adolescents:
- Oral: 7 to 13 mg/kg/day divided every 6 to 12 hours.
- The maximum daily dose: 600 mg/day.

Pregnancy Risk Factor D

Demeclocycline can cross the placenta.
The accumulation of tetracyclines in the developing teeth and long tubular bone can be observed.
In utero prolonged or repeated exposure can cause permanent discoloration (yellow-gray, brown).
Tetracyclines should be avoided during pregnancy. They are second-line antibiotics.
It is not recommended to use demeclocycline in Rocky Mountain Spotted Fever or Q fever during pregnancy.
Alternate agents in dermatological infections are preferable to demeclocycline when there is a need for systemic antibiotics.

Demeclocycline use during breastfeeding:

Breast milk contains tetracyclines.
Breast milk can cause a non-dose-related alteration of the bowel flora.
Tetracyclines should not be used by breastfeeding mothers as they can cause permanent tooth staining.
Sources say that breastfeeding can be continued while receiving tetracycline therapy, but it is best to use alternative agents whenever possible.
Breastfeeding women should avoid prolonged tetracyclines treatment (eg, to treat acne).
It is important to monitor infants for GI disorders.
There are potential adverse events.
The decision to breastfeed or not during therapy is based on the risks to the infant and the benefits to the mother, as determined by the manufacturer.

Demeclocycline (Declomycin) dose adjustment in renal disease:

There are no specific dosage adjustments provided in the manufacturer’s labeling, use with caution.
An increase in the time interval between doses or dose reduction is recommended.
Tetracyclines are not removed in significant quantities by hemodialysis or peritoneal dialysis.

Demeclocycline (Declomycin) dose adjustment in liver disease:

There are no specific dosage adjustments provided in the manufacturer’s labeling, although use with caution.
An increase in the time interval between doses or dose reduction is recommended.

Side effects of demeclocycline:

Cardiovascular:
- Pericarditis
Central Nervous System:
- Bulging Fontanel (Infants)
- Dizziness
- Headache
- Pseudotumor Cerebri (Adults)
Dermatologic:
- Erythema Multiforme
- Erythematous Rash
- Maculopapular Rash
- Skin Photosensitivity
- Skin Pigmentation
- Urticaria
Endocrine & Metabolic:
- Microscopic Thyroid Discoloration (Brown/Black)
- Nephrogenic Diabetes Insipidus
Gastrointestinal:
- Anorexia
- Dental Discoloration
- Diarrhea
- Dysphagia
- Enterocolitis
- Esophageal Ulcer
- Glossitis
- Nausea
- Pancreatitis
- Vomiting
Genitourinary:
- Balanitis
- Inflammatory Anogenital Lesion (With Monilial Overgrowth)
Hematologic & Oncologic:
- Eosinophilia
- Hemolytic Anemia
- Iga Vasculitis
- Neutropenia
- Thrombocytopenia
Hepatic:
- Increased Liver Enzymes
Hypersensitivity:
- Anaphylaxis
- Angioedema
Infection:
- Superinfection
Neuromuscular & Skeletal:
- Exacerbation Of Systemic Lupus Erythematosus
- Lambert-Eaton Syndrome
- Lupus-Like Syndrome
- Polyarthralgia
Ophthalmic:
- Visual Disturbance
Otic:
- Tinnitus
Renal:
- Acute Renal Failure
- Increased Blood Urea Nitrogen
Respiratory:
- Pulmonary Infiltrates

Contraindications to Demeclocycline (Declomycin):

Allergy reactions to demeclocycline, Tetracyclines or any component of this formulation

Warnings and precautions

CNS effects
- Demeclocycline may cause dizziness, blurred sight, or lightheadedness. This can lead to impairment of mental or physical abilities.
- Patients should be cautious when operating machinery or driving.
Diabetes insipidus syndrome
- Demeclocycline may cause dose-dependent nephrogenic diabeticus insipidus.
- This condition is reversible upon discontinuation. However, this adverse effect of demeclocycline was used as a therapeutic advantage for hyponatremia associated to SIADH.
BUN Increased
- Patients with renal dysfunction should not use it. It has anti-anabolic properties that can cause increased BUN levels.
Intracranial hypertension (eg pseudotumor cerebri).
- Intracranial hypertension can present with blurred vision, headaches and blurred vision.
- It is treatable by withdrawing but permanent sequelae may be possible.
Photosensitivity
- Photosensitivity is possible.
- Skin erythema should not be treated with drugs.
- Avoid prolonged sun exposure and use sunscreen. Avoid using tanning agents.
Superinfection
- Long-term therapy can be used to treat fungal or bacterial superinfections, such as C. difficile-associated diarrhea, (CDAD), and pseudomembranous collitis.
- CDAD was observed for >2 months after antibiotic treatment.
Hepatic impairment
- Patients with hepatic impairment should exercise caution when adjusting their doses and/or adjusting the interval frequency.
- It is rare for it to cause hepatotoxicity or hepatic failure.
Renal impairment
- It is important to adjust the dosage and/or adjust the interval frequency with caution.
- It can cause nephrotoxicity, especially in the setting of cystic fibrosis.

Demeclocycline: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Aminolevulinic Acid Topical	Photosensitizing agents may increase the photosensitizing effects of Aminolevulinic Acid Topical.
BCG Vaccine (Immunization)	Antibiotics can decrease the therapeutic effects of BCG Vaccine (Immunization).
Desmopressin	Demeclocycline can decrease the therapeutic effects of Desmopressin.
Lactobacillus & Estriol	Antibiotics can reduce the therapeutic effects of Lactobacillus or Estriol.
Magnesium Dimecrotate	Tetracyclines may interact through an unknown mechanism.
Mipomersen	The hepatotoxic effects of Mipomersen may be enhanced by Tetracyclines.
Neuromuscular-Blocking Agents	Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
Porfimer	Photosensitizing agents may increase the photosensitizing effects of Porfimer.
Verteporfin	Photosensitizing agents may increase the photosensitizing effects of Verteporfin.
Vitamin K antagonists (eg warfarin)	Vitamin K Antagonists may have an anticoagulant effect that is enhanced by Tetracyclines.
Risk Factor D (Consider therapy modifications)
Antacids	Reduces the absorption Tetracyclines. Management: It is possible to separate the administration of oral tetracycline derivatives and antacids for several hours, if necessary, in order to reduce the potential for interaction.
Bile Acid Sequestrants	Might decrease Tetracycline absorption.
Bismuth Subcitrate	Could cause a decrease in serum Tetracycline concentrations. Management: Do not administer oral tetracyclines to patients within 30 minutes after receiving bismuth subcitrate. This is not recommended for all regimens that are intended to treat H. Pylori infections.
Bismuth Subsalicylate	This may cause a decrease in serum Tetracycline concentrations. Management: Tetracyclines should be taken 2 hours or 6 hours before bismuth. It is not necessary to separate doses in Helicobacter Pylori eradication regimens.
Calcium Salts	Can decrease serum levels of Tetracyclines. Management: If oral calcium and oral tetracyclines cannot be avoided, it is worth seperating the administration for several hours.
Iron Salts	Iron salts may be less absorbed by Tetracyclines. The serum concentration of Tetracyclines may be decreased by Iron Salts. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Isomaltoside; Iron Sucrose.
Lanthanum	Can decrease serum concentrations of Tetracyclines. Treatment: Oral tetracycline antibiotics should be administered at least 2 hours before or after lanthanum.
Magnesium Salts	Tetracyclines may be less absorbed. Only applicable to oral preparations.
Multivitamins/Minerals (with ADEK, Folate, Iron)	Can decrease serum levels of Tetracyclines. Management: If oral tetracyclines and a multivitamin polyvalent cation-containing multivitamin cannot be avoided, separate administration may be necessary.
Multivitamins/Minerals (with AE, No Iron)	Can decrease serum levels of Tetracyclines. Management: If oral tetracyclines and a multivitamin polyvalent cation-containing multivitamin cannot be avoided, separate administration may be necessary.
Penicillin	Penicillin's therapeutic effects may be diminished by Tetracyclines.
Quinapril	Can decrease serum levels of Tetracyclines. To reduce the chance of interactions, administer separate doses of quinapril. If these products are combined, monitor for decreased efficacy of tetracycline.
Sodium Picosulfate	Antibiotics can reduce the therapeutic effects of Sodium Picosulfate. Patients who are currently using or have just finished using antibiotics should consider using an alternative product to cleanse the bowels before undergoing a colonoscopy.
Sucralfate	Reduces Tetracycline absorption To minimize the effects of the interaction, administer the tetracycline derivative at the least two hours before sucralfate.
Sucroferric Oxyhydroxide	Could cause a decrease in serum Tetracycline concentrations. Administration: Oral/enteral doxycycline should be administered at least one hour before sucroferric Oxyhydroxide. There are no current guidelines regarding the dosage of other tetracyclines. Parenteral administration of Tetracyclines is not expected to cause any interaction.
Typhoid Vaccine	The therapeutic effects of Typhoid vaccine may be diminished by antibiotics. The only affected strain is the live attenuated Ty21a. Patients being treated with systemic antibiotics should avoid vaccination with live attenuated Typhoid vaccine (Ty21a). This vaccine should not be used until at least three days after the cessation or discontinuation of antibacterial agent treatment.
Zinc Salts	Could decrease Tetracycline absorption. This is only a concern if both products are taken orally. Management: Doxycycline is a non-interacting tetracycline derivative. To minimize interactions, it is important to separate oral tetracycline derivative from oral zinc salts for at least two hours. Zinc chloride is an exception.
Risk Factor X (Avoid Combination)
Aminolevulinic Acid Systemic	The photosensitizing effects of Aminolevulinic Acid Systemic may be enhanced by the use of photosensitizing agents.
BCG (Intravesical).	The therapeutic effects of BCG (Intravesical) may be diminished by antibiotics
Cholera Vaccine	Cholera Vaccine may be less effective if taken with antibiotics. Treatment: Cholera vaccine should be avoided in patients who have received systemic antibiotics.
Mecamylamine	Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine.
Methoxyflurane	Tetracyclines could increase the nephrotoxic effects of Methoxyflurane.
Retinoic Acid Derivatives	Tetracyclines could increase the toxic/adverse effects of Retinoic acid Derivatives. Pseudotumor cerebri is a concern. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical).
Strontium Ranelate	Could decrease serum concentrations of Tetracyclines. Management: To minimize the potential effects of strontium Ranelate on tetracycline concentrations, it's recommended that strontium runelate treatment is stopped during tetracycline therapy.

Monitoring parameters:

CBC
Liver function tests
Renal function tests

How to administer Demeclocycline (Declomycin)?

It should be given orally 1 hour before or 2 hours after food or milk.
In order to minimize the risk of esophageal irritation and ulceration, it should be swallowed with plenty of fluids.

Mechanism of action of Demeclocycline (Declomycin):

Demeclocycline inhibits protein synthesis by binding to the 30S or 50S ribosomal units of the susceptible bacteria.
It can cause cytoplasmic membrane damage and inhibition of ADH in patients suffering from chronic SIADH.

The onset of action in the treatment of SIADH: