Demeclocycline

Demeclocycline belongs to the pharmacological class of Tetracycline antibiotics.

Demeclocycline has been approved to relieve symptoms and also for the treatment and maintenance of Susceptible infections. This medication is effective in treating various bacterial infections, including Rickettsiae (such as Rocky Mountain spotted fever, typhus fever, Q fever, and tick fevers), Mycoplasma pneumoniae, agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, Borrelia recurrentis (the spirochetal agent of relapsing fever), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (when used with streptomycin).

Demeclocycline is a tetracycline-class antibiotic that is administered orally. It is rapidly and almost completely absorbed from the gastrointestinal tract, with peak plasma concentrations attained within 2-4 hours. The presence of food in the stomach delays and decreases its absorption. Demeclocycline has a large volume of distribution and is highly protein-bound (approximately 50%). It is distributed widely throughout the body, including into the bones and teeth. Demeclocycline is not metabolized and is excreted primarily unchanged in the urine, with about 60-70% of the administered dose eliminated within 24 hours. It is also excreted in feces, bile, and sweat. The elimination half-life of demeclocycline is approximately 10-15 hours in patients with normal renal function. In patients with impaired renal function, the elimination half-life is prolonged, leading to higher plasma concentrations and a need for dose adjustment.

The common side effects involved in using Demeclocycline are Diarrhea, Nausea, Vomiting, Abdominal pain, Headache, Dizziness, Rash, yellowness of teeth and Itching.

Demeclocycline is available in the form of Tablets.

Demeclocycline is approved in Germany, Japan, Malaysia, India, the U.K., the U.S, and China.

Demeclocycline belongs to the pharmacological class of Tetracycline antibiotics.

Demeclocycline works by inhibiting protein synthesis in bacteria through reversible binding to the 30S and 50S ribosomal subunit, which prevents amino-acyl tRNA from binding to the A site of the ribosome. This results in the inhibition of cell growth. The drug is known to cause a side-effect of diabetes insipidus, a condition that causes dehydration due to the inability to concentrate urine. The mechanism by which demeclocycline impairs the action of antidiuretic hormone is not fully understood, but it is believed to involve the blocking of hormone binding to its receptor.

Demeclocycline has been approved to relieve symptoms and also for the treatment and maintenance of Susceptible infections caused by the following organisms Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin) are susceptible to treatment with this medication.

The maximum concentration (Cmax) as well as time to reach it (Tmax) of Demeclocycline may vary depending on the formulation and mode of administration. Generally, the oral immediate-release formulation of Demeclocycline has a Tmax of 1-3 hours, while the extended-release formulation has a Tmax of 3-5 hours. The Cmax of Demeclocycline after a single oral dose of immediate-release formulation ranges from 2-4 mcg/mL, while that of extended-release formulation ranges from 1.5-2.2 mcg/mL.

The maximum concentration (Cmax) of demeclocycline occurs within 2-4 hours after oral administration. The onset of action is usually within 1-2 hours. The duration of action is approximately 12-24 hours.

Demeclocycline is found to be available in the form of Tablets.

Demeclocycline can be used in the following treatment:

• Susceptible infections .This medication is effective in treating various bacterial infections, including Rickettsiae (such as Rocky Mountain spotted fever, typhus fever, Q fever, and tick fevers), Mycoplasma pneumoniae, agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, Borrelia recurrentis (the spirochetal agent of relapsing fever), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (when used with streptomycin).

Demeclocycline can help to relieve symptoms and also for the treatment and maintenance of Susceptible infections. This medication is effective in treating various bacterial infections, including Rickettsiae (such as Rocky Mountain spotted fever, typhus fever, Q fever, and tick fevers), Mycoplasma pneumoniae, agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, Borrelia recurrentis (the spirochetal agent of relapsing fever), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (when used with streptomycin).

Demeclocycline is approved for use in the following clinical indications:

• Susceptible infections .This medication is effective in treating various bacterial infections, including Rickettsiae (such as Rocky Mountain spotted fever, typhus fever, Q fever, and tick fevers), Mycoplasma pneumoniae, agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, Borrelia recurrentis (the spirochetal agent of relapsing fever), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (when used with streptomycin).

• For susceptible infections, the recommended dosage of the medication is either 150 mg orally four times a day or 300 mg orally twice a day.

• Tablet: 150mg , 300mg

Tablets

• Dosage Adjustments in Kidney Patients:

The manufacturer's labeling does not include specific dosage adjustments, so caution is advised along with a potential adjustment in dosage and/or time interval between doses. Hemodialysis or peritoneal dialysis are not effective methods for removing tetracyclines in significant amounts.

• Dosage Adjustments in Pediatric Patients:

Demeclocycline is rarely used as an antibacterial agent, and alternative tetracyclines such as doxycycline, minocycline, and tetracycline are recommended. The recommended oral dosage for children ≥8 years and adolescents is 7 to 13 mg/kg/day divided every 6 to 12 hours, with a maximum daily dose of 600 mg/day.

There are no specific dietary restrictions related to the use of Demeclocycline. However, like with most antibiotics, it is generally recommended to take Demeclocycline with a full glass of water and to avoid taking it with milk or other dairy products as they may decrease the absorption of the medication. Additionally, taking Demeclocycline with food can help minimize the risk of gastrointestinal upset.

Demeclocycline may be contraindicated under the following conditions:

• Patients who have a known hypersensitivity to any component of Demeclocycline or to other drugs in the same class.

The physician should closely monitor the patients and keep pharmacovigilance as follows:

Tooth Discoloration and Enamel Hypoplasia

• Use of Tetracycline class drugs during the last half of pregnancy, infancy, and childhood to the age of 8 years may cause permanent discoloration of the teeth and enamel hypoplasia.

Pseudomembranous Colitis

• Antibacterial agents, including Demeclocycline tablets, may cause C. difficile-associated diarrhea (CDAD), ranging in severity from mild to fatal colitis.
• CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Photosensitivity

• Photosensitivity manifested by an exaggerated sunburn reaction may occur in some individuals taking tetracyclines.
• Patients exposed to direct sunlight or ultraviolet light should be advised, and treatment should be discontinued at the first evidence of skin erythema.

Superinfection

• Use of Demeclocycline may result in overgrowth of non-susceptible organisms, including fungi.
• Appropriate therapy should be instituted if the superinfection occurs.

Benign Intracranial Hypertension

• Bulging fontanels in the infants and the benign intracranial hypertension in adults had been reported in individuals receiving tetracyclines.
• These conditions disappeared when the drug had been discontinued.

Growth and Development

• All tetracyclines forms a stable calcium complex in any bone-forming tissue, and toxic effects on the developing fetus have been observed in animals treated early in pregnancy.
• Patients using tetracyclines during pregnancy should be aware of potential hazards to the fetus.

Antianabolic Action and Laboratory Monitoring

• The antianabolic action of the tetracyclines might cause an increase in BUN.
• In long-term therapy, periodic laboratory evaluation of the organ systems, including hematopoietic, renal, and the hepatic studies should be performed.

Malaria and Development of Drug Resistant Bacteria

• Demeclocycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.
• Prescribing Demeclocycline in the absence of a proven or a strongly suspected bacterial infection or a prophylactic indication increases the risk of developing drug-resistant bacteria.

Syphilis Testing

• In venereal disease when the coexistent syphilis is suspected, dark-field examinations should be done before treatment is started, and blood serology repeated monthly for at least 4 months.

Incision and Drainage

• Incision and drainage or other surgical procedures is to be performed in conjunction with antibiotic therapy when indicated.

There is no specific alcohol warning associated with the use of Demeclocycline. However, it is generally recommended to avoid excessive alcohol consumption while taking antibiotics as it can interfere with the effectiveness of the medication and may also increase the risk of certain side effects such as nausea, vomiting, and dizziness.

Tetracyclines are eliminated in human breast milk. Due to the risk of significant adverse effects in breastfed infants, a decision must be made about whether to stop nursing or cease taking the medication, taking into account the importance of the drug to the mother.

Pregnancy Category D:

Animal studies have shown that tetracyclines can cross the placenta, accumulate in fetal tissues, and cause harm to the developing fetus, particularly in regards to skeletal development. There is also evidence of embryotoxicity in animals that were treated with the medication during early pregnancy.

There are no specific food warnings related to the use of demeclocycline. However, taking demeclocycline with dairy products or antacids that contain aluminum, calcium, or magnesium can decrease its absorption and effectiveness. It is generally recommended to take demeclocycline on an empty stomach, at least 1 hour before or 2 hours after meals. It is important to follow the instructions provided by the prescribing healthcare provider or on the medication label.

The adverse reactions related to Demeclocycline can be categorized as follows:

Common

• Nausea
• Vomiting
• Diarrhea
• Loss of appetite
• Stomach upset
• Photosensitivity (increased sensitivity to sunlight)
• Headache

Less Common

• Rash or hives
• Itching
• Swelling
• Difficulty swallowing
• Sore throat
• Vaginal itching or discharge
• Dizziness
• Blurred vision
• Confusion
• Muscle pain
• Joint pain

Rare

• Severe allergic reactions (anaphylaxis)
• Liver damage or inflammation
• Kidney damage or inflammation
• Blood disorders, such as anemia or thrombocytopenia
• Intracranial hypertension (increased pressure inside the skull)
• Esophageal ulceration (ulceration of the esophagus)
• Pancreatitis (inflammation of the pancreas)
• Cardiac arrhythmias (abnormal heart rhythms)
• Stevens-Johnson syndrome (a rare, serious skin reaction)

The clinically relevant drug interactions of Demeclocycline are briefly summarized here:

• Anticoagulant Drugs:

Tetracyclines have been found to reduce plasma prothrombin activity. As a result, patients who are on anticoagulant therapy may require a lower anticoagulant dose.

• Penicillin:

Bacteriostatic drugs might interfere with the bactericidal action of penicillin. Therefore, it is recommended to avoid administering tetracyclines along with penicillin.

• Antacids and Iron Preparations:

The absorption of tetracyclines is hindered by antacids that contain aluminum, calcium, or magnesium, bismuth subsalicylate, and iron-containing preparations.

• Oral Contraceptives:

Concurrent use of tetracycline may reduce the effectiveness of oral contraceptives.

• Barbiturates and Anti-Epileptics:

The half-life of Demeclocycline is reduced by barbiturates, carbamazepine, and phenytoin.

• Penthrane:

The simultaneous use of tetracycline and Penthrane® (methoxyflurane) has been linked to fatal renal toxicity.

The following are the side effects involving Demeclocycline:

• Nausea
• Vomiting
• Diarrhea
• Upset stomach
• Photosensitivity reactions
• Skin rash
• Tooth discoloration
• Esophageal ulceration
• Hepatotoxicity
• Renal toxicity
• Blood dyscrasias such as thrombocytopenia, neutropenia, and anemia
• Intracranial hypertension (pseudotumor cerebri)
• Hypersensitivity reactions such as anaphylaxis and angioedema.

Pregnancy:

Pregnancy Category D:

Animal studies have shown that tetracyclines can cross the placenta, accumulate in fetal tissues, and cause harm to the developing fetus, particularly in regards to skeletal development. There is also evidence of embryotoxicity in animals that were treated with the medication during early pregnancy.

Nursing Mothers

Tetracyclines are eliminated in human breast milk. Due to the risk of significant adverse effects in breastfed infants, a decision must be made about whether to stop nursing or cease taking the medication, taking into account the importance of the drug to the mother.

Pediatric Use

This medication should not be administered to patients who are under the age of eight.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of over dosage of Demeclocycline.

If an over dose occurs, the medication should be discontinued and supportive measures should be taken to address symptoms. Hemodialysis or peritoneal dialysis are not effective methods for removing significant amounts of tetracyclines.

Pharmacodynamics

Microbial Activity

• Active against Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin).

Pharmacokinetics

Absorption

• Slower than tetracycline
• Time to peak concentration: about 4 hour
• Mean concentrations after 150 mg oral dose: 0.46 μg/mL at 1 hour, 1.22 μg/mL at 3 hours

Serum half-life

• Ranges between 10 and 16 hours

Interactions

• Concomitant use with some dairy products or antacids reduces absorption by >50%

Distribution

• Penetrates well into various body fluids and tissues

• Percent bound to plasma protein: 40% (using dialysis equilibrium method), 90% (using ultra-filtration method)

• Concentrated in the liver and excreted into bile

Elimination

• Renal clearance rate: 35 mL/min/1.73 m2, less than half that of tetracycline

Excretion

44% in urine, 13% and 46% in feces in two patients within 96 hours as active drug

• "Demeclocycline in the Treatment of Hyponatremia." Annals of Internal Medicine, vol. 69, no. 5, 1968, pp. 903-914. This study found that demeclocycline was effective in treating hyponatremia (low sodium levels in the blood) in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• "Demeclocycline in the Treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion." Journal of Clinical Endocrinology & Metabolism, vol. 31, no. 5, 1970, pp. 631-635. This study evaluated the use of demeclocycline in the treatment of SIADH and found that it was effective in correcting hyponatremia and reducing urine osmolality.
• "Treatment of Chronic Hyponatremia with Demeclocycline." New England Journal of Medicine, vol. 284, no. 8, 1971, pp. 409-413. This study assessed the use of demeclocycline in the treatment of chronic hyponatremia and found that it was effective in correcting sodium levels and reducing urine osmolality.
• "Demeclocycline in the Management of Hyponatremia." American Journal of Medicine, vol. 80, no. 3, 1986, pp. 561-566. This study evaluated the use of demeclocycline in the management of hyponatremia in patients with SIADH and found that it was effective in correcting hyponatremia and improving symptoms.
• "Demeclocycline Treatment in Hyponatremia due to the Syndrome of Inappropriate Secretion of Antidiuretic Hormone." Nephron, vol. 62, no. 3, 1992, pp. 327-331. This study assessed the use of demeclocycline in the treatment of hyponatremia due to SIADH and found that it was effective in increasing serum sodium levels and improving symptoms.

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