Demeclocycline

Demeclocycline

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.

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 such as 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.

Patricia L. Bounds, Ph.D.

KEY TERMS

Anaphylactoid purpura

—A short-term allergic condition of blood vessels, found chiefly in children, that is characterized by wet sores on the skin of the buttocks, legs, and lower abdomen. Joint pain, stomach bleeding, and blood in the urine are also common findings. The disease, also called Henoch-Schonlein (Schonlein-Henoch) purpura, usually lasts for about 6 weeks and has no long-term effects unless kidney involvement is severe.

Anaphylaxis

—A severe allergic reaction to a foreign substance (antigen) that a patient has had previous contact with, characterized by redness and swelling, itching, water build-up, and, in severe cases, extremely low blood pressure, lung spasms, and shock.

Angioedema

—A sudden, painless, swelling of short duration that can affect the face, neck, lips, throat, hands, feet, genitals, or abdominal organs; also called angioneurotic edema.

Antidiuretic hormone

—A peptide hormone, also called vasopressin, synthesized in the hypothalamus and released by the posterior pituitary gland in response to decreased blood volume, that stimulates capillary muscles and concentrates and reduces the elimination of urine.

Benign intracranial hypertension

—Also called pseudotumor cerebri or meningeal hydrops, a condition of swelling of the optic nerve and mild paralysis of the cranial nerves, with headache, nausea, and vomiting.

Dysphagia

—Difficulty in swallowing.

Hyponatremia

—A condition in which the serum sodium concentration falls to less than 135 milliequivalents per liter (mEq/L), caused by too little excretion of water or by too much water in the bloodstream; in severe cases, hyponatremia leads to water intoxication, characterized by confusion, lethargy, muscle spasms, convulsions, and coma.

Lupus erythematosus

—A long-term disease that affects women four times more often than men, characterized by severe swelling of the blood vessels giving rise to arthritis, kidney disorders, red rash over the nose and cheeks, weakness, fatigue, weight loss, photosensitivity, fever, and skin sores that may spread to the mucous membranes and other tissues of the body; also called systemic or disseminated lupus erythematosus.

Nephrogenic diabetes insipidus

—A condition in which the kidneys do not retain urine, resulting in excess urination and thirst, and very watered-down urine.

Pancreatitis

—An inflammation of the pancreas diagnosed on the basis of severe pain that begins in the abdomen and moves to the back, fever, loss of appetite, nausea, vomiting, and jaundice.

Pericarditis

—An inflammation of the pericardium, the membrane covering the heart, marked by pain that begins in the chest and moves to the shoulder or neck, fever, difficulty breathing, and a dry cough.

Photosensitivity

—An abnormal sensitivity of the skin to ultraviolet light, often resulting from use of an oral or topical drug, that leads to accelerated and severe burning and blistering of the skin.

Prothrombin

—A plasma protein, produced by the liver and converted to thrombin by activation factors in the plasma, involved in blood coagulation; also called factor II.

Superinfection

—An overgrowth, during antimicrobial treatment for another infection, of a microorganism not affected by the treatment.

Tetracycline

—A broad-spectrum antibiotic.

Tinnitus

—A sensation of ringing or other similar sound in the ears.