Declostatin

Uses

Atypical pneumonia, Hyponatraemia, Pneumonia, Susceptible infections

Declostatin is also used to associated treatment for these conditions: Actinomycosis, Anthrax, Bartonellosis, Brucellosis, Campylobacter Infection, Chlamydia Trachomatis Infection, Chlamydial Infections, Cholera, Clostridium Difficile Infection (CDI), Conjunctivitis caused by chlamydia, Gram-negative infections Bacterial Infections, Listeria infection, Necrotizing ulcerative gingivostomatitis, Plague, Psittacosis, Relapsing fever caused by Borrelia recurrentis, Respiratory Tract Infections (RTI), Rickettsia Infections, Severe Acne Vulgaris, Sexually Transmitted Infections (STIs), Skin infection caused by Staphylococcus aureus, Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), Tularemia, Urinary Tract Infection, Yaws, Acute Intestinal amebiasis

How Declostatin works

Declostatin inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.

Dosage

Declostatin dosage

Chronic hyponatraemia associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH):

• Adult:Initially, 900-1,200 mg daily in divided doses. Maintenance: 600-900 mg daily in divided doses.
• Child:Not recommended for childn <12 yr.

Susceptible infections:

• Adult:600 mg daily in 2 or 4 divided doses.
• Child:Not recommended for childn <12 yr.

Atypical pneumonia:

• Adult:900 mg daily in 3 divided doses for 6 days.
• Child:Not recommended for childn <12 yr.

Should be taken on an empty stomach. Take with a full glass of water on an empty stomach at least 1 hr before or 2 hr after meals.

Side Effects

Photosensitivity, reversible nephrogenic diabetes insipidus, permanent discolouration of the teeth, brownish-black microscopic discolouration of thyroid tissue, nausea, vomiting, diarrhoea, increases in LFT values, hepatitis, jaundice, hepatic failure, rashes, pruritus, bullous dermatoses, exfoliative dermatitis, skin discolouration, pseudotumour cerebri in adults and bulging fontanelles in infants, headache, dizziness, visual disturbances, impaired hearing, urticaria, angioneurotic oedema, pericarditis, anaemia, thrombocytopenia, neutropenia, agranulocytosis, eosinophilia.

Toxicity

Oral, rat: LD₅₀ = 2372 mg/kg

Precaution

Patients with pre-existing SLE and myasthenia gravis. Hepatic and renal impairment. Pregnancy.

Interaction

Reduced absorption with antacids containing Al, Mg, or Ca, Fe-containing preparations, zinc, kaolin, quinapril, strontium ranelate, sucralfate, tripotassium dicitratobismuthate. May reduce the efficacy of oral contraceptives and penicillins. Increased risk of benign intracranial HTN with retinoids (e.g. acitretin, isotretinoin, tretinoin). Increased risk of ergotism with ergotamine and methysergide. May inactivate oral typhoid vaccine. May potentiate the effect of anticoagulants.

Food Interaction

• Avoid milk and dairy products.
• Avoid multivalent ions.
• Take on an empty stomach.

[Moderate] ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption.

The calcium content of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

Declostatin multivitamins interaction

[Moderate] GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration.

Therapeutic failure may result.

The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract.

In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%.

In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%.

Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg.

Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline.

Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally.

It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

Coadministration of a tetracycline with any iron-containing product should be avoided if possible.

Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

Declostatin Drug Interaction

Moderate: calcium / vitamin d, calcium / vitamin dMinor: furosemide, furosemideUnknown: fluticasone / salmeterol, fluticasone / salmeterol, aspirin, aspirin, lorazepam, lorazepam, carvedilol, carvedilol, duloxetine, duloxetine, polyethylene glycol 3350, polyethylene glycol 3350, levothyroxine, levothyroxine, cholecalciferol, cholecalciferol

Declostatin Disease Interaction

Major: colitisModerate: diabetes insipidus syndrome, hepatotoxicity, renal dysfunction, esophageal irritation

Elimination Route

Tetracyclines are readily absorbed.

Half Life

10-17 hours

Clearance

• Renal cl=35 mL/min/1.73 m2

Elimination Route

Declostatin 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. 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.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Hypersensitivity to demeclocycline or other tetracyclines. Lactation. Concurrent use with methoxyflurane.

Special Warning

Hepatic Impairment: Max: 1 gm daily.

Storage Condition

Store between 20-25° C.

Innovators Monograph

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