Usage
Demeclocycline is an antibiotic belonging to the tetracycline class. It is prescribed for the treatment of various bacterial infections caused by susceptible organisms, including:
- Respiratory tract infections: Pneumonia, bronchitis
- Urinary tract infections
- Skin and soft tissue infections
- Sexually transmitted infections (STIs): Syphilis, gonorrhea (though no longer a preferred treatment), chancroid, granuloma inguinale, lymphogranuloma venereum
- Other infections: Brucellosis (in combination with streptomycin), plague, cholera, tularemia, relapsing fever, Q fever, Rocky Mountain spotted fever, typhus fever, psittacosis, melioidosis, glanders, yaws, actinomycosis, gas gangrene, tetanus, acute intestinal amebiasis, severe acne vulgaris (as adjunctive therapy)
Demeclocycline’s pharmacological classification is antibiotic.
Mechanism of Action: Demeclocycline inhibits bacterial protein synthesis by reversibly binding to the 30S and 50S ribosomal subunits, preventing aminoacyl-tRNA from binding to the A site of the ribosome.
Additionally, demeclocycline is used off-label to treat syndrome of inappropriate antidiuretic hormone secretion (SIADH), a condition characterized by excessive water retention. This is due to its ability to induce reversible nephrogenic diabetes insipidus.
Alternate Names
- Generic Name: Demeclocycline hydrochloride
- Brand Name: Declomycin
How It Works
Pharmacodynamics: Demeclocycline exerts its bacteriostatic effect by inhibiting bacterial protein synthesis. It does not directly kill bacteria but prevents their growth and replication, allowing the body’s immune system to eliminate the infection. In SIADH, Demeclocycline antagonizes the antidiuretic hormone (ADH) in the renal tubules, promoting water excretion and correcting hyponatremia.
Pharmacokinetics:
- Absorption: Demeclocycline is absorbed orally, but its absorption is reduced by food, milk, and dairy products, antacids containing aluminum, magnesium, or calcium, iron supplements and multivitamins with iron, as well as laxatives with magnesium
- Distribution: It is widely distributed throughout the body, crossing the placental barrier and entering breast milk.
- Metabolism: Demeclocycline undergoes partial hepatic metabolism.
- Elimination: It is primarily excreted in the urine and feces, with a half-life of 10-17 hours. It is not significantly removed by hemodialysis or peritoneal dialysis.
Mode of Action: Demeclocycline passively diffuses through bacterial cell membranes, binding to the 30S and 50S ribosomal subunits to prevent protein synthesis.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Demeclocycline primarily targets bacterial ribosomes. In SIADH treatment, it antagonizes ADH action in the renal tubules.
Elimination Pathways: Renal and fecal excretion, with partial hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Bacterial Infections: 150 mg orally every 6 hours or 300 mg orally every 12 hours. For primary atypical pneumonia, 900 mg/day in 3 divided doses for 6 days may be used.
- SIADH (Off-label): Initial dose: 600-1200 mg/day orally in 3 or 4 divided doses. Maintenance dose: 600-900 mg/day orally or the lowest effective dose.
Children:
- Bacterial Infections: Children older than 8 years: 7-13 mg/kg/day orally divided into 2-4 doses (maximum dose: 600 mg/day). Demeclocycline is generally avoided in children younger than 8 years due to the risk of tooth discoloration and enamel hypoplasia.
Special Cases:
- Elderly Patients: Use with caution due to the risk of increased drug levels from decreased renal clearance. Dose adjustments might be necessary.
- Patients with Renal Impairment: Reduce dose and/or prolong dosing interval.
- Patients with Hepatic Dysfunction: Reduce dose and/or prolong dosing interval. Use with caution as demeclocycline can cause hepatotoxicity.
- Patients with Comorbid Conditions: Monitor patients with systemic lupus erythematosus (SLE), myasthenia gravis, diabetes insipidus, and esophageal irritation.
Clinical Use Cases
Demeclocycline’s use in settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is limited as other antibiotic options are generally preferred. Demeclocycline does not have specific dosage recommendations for these situations.
Dosage Adjustments
Adjustments based on renal/hepatic dysfunction are described above. No specific guidelines are available for metabolic disorders or genetic polymorphisms affecting drug metabolism.
Side Effects
Common Side Effects
- Nausea, vomiting, diarrhea, loss of appetite
- Darkened skin color
- Swollen tongue
- Vaginal itching or discharge
- Headache, dizziness, lightheadedness
- Rectal discomfort
Rare but Serious Side Effects
- Hypersensitivity reactions (hives, difficulty breathing, swelling of the face or throat)
- Severe skin reactions (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling)
- Severe stomach pain, bloody diarrhea
- New or worsening cough, fever, trouble breathing
- Painful swallowing, vomiting blood
- Kidney problems (swelling, reduced urination, fatigue, shortness of breath)
- Intracranial hypertension (severe headache, blurred vision, double vision, vision loss)
- Clostridium difficile infection (severe diarrhea, abdominal pain)
- Liver damage (nausea/vomiting, abdominal pain, yellowing of skin and eyes, dark urine)
- Changes in hearing (ringing, decreased hearing)
- Easy bruising/bleeding
Long-Term Effects
- Permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia in children under 8 years and developing fetuses
- Photosensitivity (increased sunburn risk)
Adverse Drug Reactions (ADR)
All serious side effects listed above can be considered ADRs requiring immediate intervention.
Contraindications
- Hypersensitivity to demeclocycline or any tetracycline antibiotic
- Pregnancy
- Breastfeeding
- Children under 8 years of age (except in life-threatening infections where no other alternatives exist)
Drug Interactions
Demeclocycline interacts with numerous medications. Some key interactions include:
- Antacids, iron supplements, calcium supplements, magnesium-containing laxatives: Reduced absorption of demeclocycline
- Oral contraceptives: Decreased effectiveness of birth control pills
- Warfarin and other anticoagulants: Altered anticoagulant effect
- Retinoids (e.g., isotretinoin, acitretin): Increased risk of intracranial hypertension
- Methoxyflurane: Increased risk of nephrotoxicity
- Cyclosporine: Increased risk of hepatotoxicity
- Rifampicin: Decreased effectiveness of demeclocycline
Refer to a comprehensive drug interaction resource for a complete list of potential interactions.
Pregnancy and Breastfeeding
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Pregnancy: Demeclocycline is contraindicated during pregnancy due to the risk of fetal harm, including tooth discoloration, enamel hypoplasia, and skeletal abnormalities.
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Breastfeeding: Demeclocycline passes into breast milk and may affect bone and tooth development in the nursing infant. It is generally recommended to avoid demeclocycline during breastfeeding. For short-term use, monitor the infant for side effects like rash, diarrhea, or thrush.
Drug Profile Summary
- Mechanism of Action: Inhibits bacterial protein synthesis by binding to ribosomal subunits. Antagonizes ADH action in the renal tubules (in SIADH).
- Side Effects: Nausea, vomiting, diarrhea, photosensitivity, tooth discoloration (in children and fetuses), intracranial hypertension (rare).
- Contraindications: Hypersensitivity, pregnancy, breastfeeding, children under 8 years.
- Drug Interactions: Antacids, iron supplements, oral contraceptives, warfarin, retinoids, methoxyflurane.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy. Generally avoided during breastfeeding.
- Dosage: Adults: 150 mg QID or 300 mg BID for infections; 600-1200 mg/day for SIADH. Children (over 8 years): 7-13 mg/kg/day divided BID-QID.
- Monitoring Parameters: Renal function, liver function, signs of infection, intracranial pressure (if relevant), serum sodium levels (in SIADH).
Popular Combinations
- Demeclocycline + streptomycin for brucellosis
Precautions
- General Precautions: Assess renal and hepatic function before and during treatment. Screen for hypersensitivity to tetracyclines.
- Specific Populations: Avoid in pregnancy and breastfeeding. Use with caution in children older than 8 years and the elderly.
- Lifestyle Considerations: Avoid prolonged sun exposure, use sunscreen and protective clothing. Advise patients to avoid alcohol as it can increase the risk of liver damage.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Demeclocycline?
A: Adults: 150 mg four times daily or 300 mg twice daily for infections. Children (over 8 years): 7-13 mg/kg/day divided into 2-4 doses. For SIADH, adults may require 600-1200 mg/day initially, with a maintenance dose of 600-900 mg/day.
Q2: Can Demeclocycline be used during pregnancy?
A: No, demeclocycline is contraindicated during pregnancy due to potential harm to the fetus.
Q3: What are the common side effects of Demeclocycline?
A: Common side effects include nausea, vomiting, diarrhea, photosensitivity, and discoloration of teeth (in children and developing fetuses).
Q4: How does Demeclocycline work?
A: It inhibits bacterial protein synthesis by binding to the 30S and 50S ribosomal subunits. In SIADH, it antagonizes the action of ADH in the renal tubules, promoting water excretion.
Q5: What are the serious side effects of Demeclocycline?
A: Serious side effects include severe skin reactions, C. difficile infection, intracranial hypertension, hepatotoxicity, and nephrotoxicity.
Q6: What drug interactions should I be aware of with Demeclocycline?
A: Demeclocycline can interact with antacids, iron supplements, oral contraceptives, anticoagulants, and retinoids, among others.
Q7: How should I counsel patients about Demeclocycline?
A: Advise patients to take demeclocycline on an empty stomach, avoid sun exposure, and report any signs of adverse effects. Counsel women of childbearing potential on the importance of contraception during treatment.
Q8: Can Demeclocycline be used in children?
A: Demeclocycline is generally avoided in children under 8 years due to the risk of tooth discoloration. In older children, dosage is weight-based.
Q9: What is the role of Demeclocycline in treating SIADH?
A: It induces a reversible form of nephrogenic diabetes insipidus, promoting increased urination and correction of hyponatremia.
