DARANIDE* (Dichlorphenamide) is an oral carbonic anhydrase inhibitor. Dichlorphenamide, a dichlorinated benzenedisulfonamide, is known chemically as 4,5-dichloro-1,3-benzenedisulfonamide. Its empirical formula is C 6 H 6 Cl 2 N 2 O 4 S 2 and its structural formula is:
Dichlorphenamide is a white or practically white, crystalline compound with a molecular weight of 305.16. It is very slightly soluble in water but soluble in dilute solutions of sodium carbonate and sodium hydroxide. Dilute alkaline solutions of dichlorphenamide are stable at room temperature.
DARANIDE is supplied as tablets, for oral administration, each containing 50 mg dichlorphenamide. Inactive ingredients are D&C Yellow 10, lactose, magnesium stearate, and starch.
*Registered trademark of MERCK & CO., INC.
Carbonic anhydrase inhibitors reduce intraocular pressure by partially suppressing the secretion of aqueous humor (inflow), although the mechanism by which they do this is not fully understood. Evidence suggests that HCO 3 - ions are produced in the ciliary body by hydration of carbon dioxide under the influence of carbonic anhydrase and diffuse into the posterior chamber with Na + ions. The aqueous fluid contains more Na + and HCO 3 - ions than does plasma and consequently is hypertonic. Water is attracted to the posterior chamber by osmosis. Systemic administration of a carbonic anhydrase inhibitor has been shown to inactivate carbonic anhydrase in the ciliary body of the rabbit's eye and to reduce the high concentration of HCO 3 - ions in ocular fluids. As is the case with all carbonic anhydrase inhibitors, DARANIDE in high doses causes some decrease in renal blood flow and glomerular filtration rate.
In man, DARANIDE begins to act within an hour and maximal effect is observed in two to four hours. The lowered intraocular tension may be maintained for approximately 6 to 12 hours.
For adjunctive treatment of: chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure.
DARANIDE is contraindicated in hepatic insufficiency, renal failure, adrenocortical insufficiency, hyperchloremic acidosis, or in conditions in which serum levels of sodium or potassium are depressed. DARANIDE should not be used in patients with severe pulmonary obstruction who are unable to increase their alveolar ventilation since their acidosis may be increased.
DARANIDE is contraindicated in patients who are hypersensitive to this product.
Potassium excretion is increased by DARANIDE and hypokalemia may develop with brisk diuresis, when severe cirrhosis is present, or during concomitant use of steroids or ACTH.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium supplements such as foods with a high potassium content. DARANIDE should be used with caution in patients with respiratory acidosis.
Caution is advised in patients receiving concomitant high-dose aspirin and carbonic anhydrase inhibitors, as anorexia, tachypnea, lethargy and coma have been rarely reported due to a possible drug interaction.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to evaluate the effects upon fertility or carcinogenic potential of DARANIDE.
Pregnancy Category C. Diclorphenamide has been shown to be teratogenic in the rat (skeletal anomalies) when given in doses 100 times the human dose. There are no adequate and well-controlled studies in pregnant women. DARANIDE should not be used in women of childbearing age or in pregnancy, especially during the first trimester, unless the potential benefits outweigh the potential risks.
It is not known whether diclorphenamide is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when diclorphenamide is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Certain side effects characteristic of carbonic anhydrase inhibitors may occur with DARANIDE, particularly with increasing doses.
The most common effects include gastrointestinal disturbances (anorexia, nausea, and vomiting), drowsiness and paresthesias.
Included in the listing which follows are some adverse reactions which have not been reported with DARANIDE. However, pharmacological similarities among the carbonic anhydrase inhibitors make it advisable to consider the following reactions when diclorphenamide is administered.
Central Nervous System/Psychiatric: ataxia, tremor, tinnitus, headache, weakness, nervousness, globus hystericus, lassitude, depression, confusion, disorientation, dizziness;
Gastrointestinal: constipation, hepatic insufficiency;
Metabolic: loss of weight, metabolic acidosis, electrolyte imbalance (hypokalemia, hyperchloremia), hyperuricemia;
Hypersensitivity: skin eruptions, pruritus, fever;
Hematologic: leukopenia, agranulocytosis, thrombocytopenia;
Genitourinary: urinary frequency, renal colic, renal calculi, phosphaturia.
The oral LD 50 of DARANIDE is 1710 and 2600 mg/kg in the mouse and rat respectively.
Symptoms of overdosage or toxicity may include drowsiness, anorexia, nausea, vomiting, dizziness, paresthesias, ataxia, tremor and tinnitus.
In the event of overdosage, induce emesis or perform gastric lavage. The electrolyte disturbance most likely to be encountered from overdosage is hyperchloremic acidosis that may respond to bicarbonate administration. Potassium supplementation may be required. The patient should be carefully observed and given supportive treatment.
DARANIDE is usually given in conjunction with topical ocular hypotensive agents. In acute angle-closure glaucoma, it may be used together with miotics and osmotic agents in an attempt to reduce intraocular tension rapidly. If this is not quickly relieved, surgery may be mandatory.
Dosage must be adjusted carefully to meet the requirements of the individual patient. A priming dose of 100 to 200 mg of DARANIDE (2 to 4 tablets) is suggested for adults, followed by 100 mg (2 tablets) every 12 hours until the desired response has been obtained. The recommended maintenance dosage for adults is 25 to 50 mg ( 1 [sol ] 2 to 1 tablet) once to three times daily.
No. 3256--Tablets DARANIDE, 50 mg each, are yellow, round, scored, compressed tablets, coded MSD 49 on one side and DARANIDE on the other. They are supplied as follows:
NDC 0006-0049-68 bottles of 100.
7870319 Issued October 1996
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