Key Terms: Anaphylactoid purpura, Anaphylaxis, Angioedema, Antidiuretic hormone, Benign intracranial hypertension, Dysphagia, Hyponatremia, Lupus erythematosus, Nephrogenic diabetes insipidus, Pancreatitis, Pericarditis, Photosensitivity, Prothrombin, Superinfection, Tetracycline.
Definition
Demeclocycline, more accurately demeclocycline hydrochloride, is a broad-spectrum antibiotic of the tetracycline family. Demeclocycline is marketed under the trade name Declomycin.
Purpose
Demeclocycline is used to treat cancer patients who have developed a condition known as syndrome of inappropriate antidiuretic hormone (SIADH). A wide variety of malignacies, especially small-cell lung cancer, as well as various other non-cancer conditions, give rise to SIADH, which is caused by overproduction of antidiuretic hormone (ADH). SIADH can also develop as a side effect of the anticancer drugs vincristine, vinblastine, cisplatin, melphalan, and cyclophosphamide. The increased ADH levels lead to insufficient elimination of water from the kidneys, and the retained water leads to dilution of the serum sodium concentration, a condition called hyponatremia. Symptoms of hyponatremia include weight gain in spite of appetite loss, fatigue, headache, and confusion. When the condition is severe or the onset sudden, the symptoms may develop into seizures or coma. Although treating the underlying cancer is the ideal approach, the metabolic imbalances may be alleviated in other ways. The tetracycline derivative demeclocycline has been found to be effective in treating SIADH.
Demeclocycline was originally approved by the Food and Drug Administration (FDA) to treat a wide variety of bacterial infections. It is thought that the tetracyclines work by preventing bacteria from synthesizing protein.
More recently, demeclocycline has been combined with hydrocortisone in a paste used by dentists to control inflammation and prevent infection in root canal and other endodontic procedures. The paste is sold under the trade name Ledermix.
Description
This tetracycline derivative is isolated from a mutant strain of the bacterium Streptomyces aureofaciens.
Demeclocycline was first investigated as a treatment for SIADH in 1976, and had become established as the treatment regimen of choice by 1986. The drug acts to interfere with the response of the kidneys to ADH and has consistently been found to be effective in treating SIADH with relatively few side effects.
Recommended Dosage
Demeclocycline hydrochloride is taken orally. It is supplied as 150 and 300 mg tablets and 150 mg capsules. The usual dosage of demeclocycline for SIADH is from 600 to 1200 mg/day, and should not exceed 2400 mg/day. Within five days of beginning the drug, the diuretic action begins, and it generally lasts for two to six days after the drug is discontinued.
Precautions
Absorption of demeclocycline is reduced when taken with food or dairy products, and thus should be given one hour before or two hours after a meal or ingestion of dairy products. The dose should be taken with 8 oz (240 mL) of water, and the last dose of the day should be taken at least one hour before bedtime.
Antacids containing aluminum, calcium, or magnesium interfere with absorption of orally administered tetracyclines and should not used by patients taking demeclocycline.
Photosensitivity reactions are more frequent and more severe with demeclocycline than with other tetracyclines. Patients should be advised that this reaction can occur and be cautioned to avoid exposure to direct sunlight or ultraviolet light.
With renal impairment, even usual doses of demeclocycline may lead to accumulation of the drug and the possibility of liver toxicity. Serum level determinations of the drug may be advisable under such conditions, and the dosage should be lower than usual.
Tetracyclines can cross the placenta and can have toxic effects on the developing fetus, and the drug is found in the milk of lactating women taking tetracyclines. Tetracyclines form a complex with calcium and act to decrease the rate of bone growth in any bone-forming tissue while the drug is being administered.
Side Effects
Dermatological
Skin reactions, including redness, swelling, rashes, and flaking or peeling of the skin can result from demeclocycline administration. Demeclocycline should be discontinued if the skin becomes swollen and reddened.
Patients taking demeclocycline are likely to be photosensitive. Phototoxic reactions occur with moderate to large doses and are characterized by severe skin burns resulting from direct exposure to sunlight.
Gastrointestinal
Demeclocycline can cause loss of appetite, nausea, vomiting, and diarrhea. Inflammations of the upper GI tract have also been reported as side effects, involving the tongue and esophagus, with resultant dysphagia, but many of these patients were found to have taken the medication immediately before going to bed. Inflammation of the small and large intestines has also been reported, and, as with all antibiotic therapy, overgrowth in the lower GI tract of other organisms, especially of the candida genus of yeast-like fungi, can lead to inflammatory lesions in the anogenital area.
Central Nervous System
Dizziness, tinnitus, benign intracranial hypertension (pseudotumor cerebri), and visual disturbances have been reported. More rarely, myasthenic (Eaton-Lambert) syndrome and muscle weakness have been reported.
Immune System
Possible allergic reactions to demeclocycline include hives, angioedema, anaphylaxis, anaphylactoid purpura, pericarditis, and worsening of systemic lupus erythematosus.
Other
Superinfection due to overgrowth of nonsusceptible organisms is a common side effect of demeclocycline administration. Renal toxicity has been reported. Acute pancreatitis and nephrogenic diabetes insipidus are possible side effects of demeclocycline treatment. Increases in liver enzymes and hepatic toxicity have been rarely observed. Blood conditions such as hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have also been reported. Individuals still undergoing tooth development (infants and children up to 8 years old, and in the fetus during the last half of pregnancy) may develop permanent yellowish-grayish-brown discoloration of the teeth and poor enamel development.
Interactions
Tetracyclines including demeclocycline can interfere with the bactericidal action of penicillins, and should not be administered together with penicillin. Tetracyclines coadministered with oral contraceptives can render oral contraceptives less effective. The activity of plasma prothrombin can be depressed by tetracyclines, thus patients on anticoagulant therapy may be required to decrease their anticoagulant dosage.
Resources
Books
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Abnormal Renal Transport Syndromes." Section 17, Chapter 229 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Antibacterial Drugs: Tetracyclines." Section 13, Chapter 153 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L. Stang. Nurse's Drug Guide 2003. Upper Saddle River, NJ: Prentice Hall, 2003.
Periodicals
Goh, K. P. "Management of Hyponatremia." American Family Physician 69 (May 15, 2004): 2387–2394.
Wicht, M. J., R. Haak, H. Schutt-Gerowitt, et al. "Suppression of Caries-Related Microorganisms in Dentine Lesions after Short-Term Chlorhexidine or Antibiotic Treatment." Caries Research 38 (September-October 2004): 436–441.
Organizations
American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000.
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA.
Other
Food and Drug Administration (FDA). "Medwatch Safety File, Declomycin Tablets."
—Patricia L. Bounds, Ph.D.; Rebecca Frey, PhD
