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PubMedDate not supplied

Artificially low hemoglobin A1c caused by use of dapsone.

OBJECTIVE: To describe a case of artifactually decreased hemoglobin Alc (HbAlc) attributable to use of dapsone. METHODS: We present a detailed case report and results of a related literature search. In addition, potential causes of artifactually lowered HbAlc values are discussed. RESULTS: A 35-year-old patient with type I diabetes had high home-monitored blood glucose values, high clinic plasma glucose determinations, increased fructosamine levels, and low HbAlc values. The lowering of the HbAlc level was associated with use of dapsone, and the decrease in HbAlc value was proportional to the dose of dapsone. A literature search revealed one previous report of artifactual lowering of the HbAlc value, in which high methemoglobin levels were found and thought to be the cause of the artifactually decreased HbA1c. CONCLUSION: By increasing methemoglobin levels and decreasing erythrocyte survival, dapsone can artifactually lower HbA1c. Clinicians should be aware of this potential side effect of dapsone.

Adult↗
PubMed2002

Haematological alterations in leprosy patients treated with dapsone.

OBJECTIVE: To evaluate the haemoglobin concentration (Hb); total white blood cell count (WBC), differential WBC count; platelet count and reticulocyte count in leprosy patients already treated with dapsone. DESIGN: A case-control study. SETTING: Specialist Hospital Ossiomo, which is a Leprosarium and Haematology laboratory, University of Benin Teaching Hospital (UBTH), Nigeria. SUBJECTS: Seventy six leprosy patients (forty males and thirty six females) age range 13-40 years on single dose dapsone. RESULTS: The haemoglobin concentration showed a marked decrease while the reticulocyte count was markedly elevated which was suggestive of haemolytic anaemia. There was also lymphocytosis in patients during pre and post dapsone therapy. CONCLUSION: Leprosy patients on a dosage of 100 mg dapsone, are prone to haemolytic anaemia. Leprosy patients should routinely have their Hb, WBC, platelet count and reticulocyte count determined, while on dapsone therapy in order to ascertain the presence of haemolysis.

Adolescent↗
PubMed1985

Inadequate prophylaxis of malaria with dapsone-pyrimethamine.

The dapsone-pyrimethamine combination (100 mg of dapsone, 12.5 mg of pyrimethamine [Folaprim; Maloprim, one tablet a week) is considered to provide adequate prophylaxis for Plasmodium falciparum malaria, but to be inadequate for the prevention of P. vivax malaria. Field trials and case reports, however, have shown the comparable efficacy of this combination in the suppression of parasitaemias caused by both parasites. In Lae, Papua New Guinea, 12 patients with clinical signs of malaria had serum concentrations of dapsone-pyrimethamine which were consistent with appropriate weekly use of this combination. The fact that 10 of these patients had P. vivax malaria supports the hitherto unsubstantiated view that dapsone-pyrimethamine can be ineffective in suppressing parasitaemias caused by this parasite. In the two patients with P. falciparum malaria, host factors rather than parasite resistance to dapsone-pyrimethamine were implicated in the development of the parasitaemias.

Adolescent↗
PubMed1989

Increased incidence in leprosy of hypersensitivity reactions to dapsone after introduction of multidrug therapy.

In order to address the question whether hypersensitivity reactions to dapsone are becoming more frequent, the clinical data of 7300 leprosy patients treated between 1949 and September 1988 at the McKean Rehabilitation Centre in Thailand were reviewed. Information from the period 1949 to 1969 was too incomplete to allow conclusions. The incidence of hypersensitivity reactions to dapsone between 1970 and 1982 was 0.3%. From 1982 (with the introduction of multidrug therapy) to September 1988, the incidence was 3.6%; a tenfold increase compared with the previous period. Of the 19 cases seen since 1982, 12 were diagnosed as Dapsone syndrome. Of a total of 13 patients seen since 1980 with Dapsone syndrome, 3 ended fatally, indicating the severity of the complication. The question is raised whether an unexplained drug interaction with rifampicin is responsible for the increase of hypersensitivity reactions to dapsone in patients treated for leprosy.

Adolescent↗
PubMed1991

Effect of dapsone on haemoglobin concentration in patients with leprosy.

Haemolysis and frank anaemia from dapsone therapy of leprosy has been long recognized. However, the frequency and severity of this side-effect have not been well documented. We report herein a retrospective analysis of the effect of daily dapsone (generally 100 mg/day) on the haemoglobin concentration of 100 leprosy patients undergoing initial chemotherapy. The average haemoglobin was found to fall significantly by almost 2 g/dl, from 14.25 +/- 1.27 g/dl to a nadir of 12.31 +/- 1.61 (P less than 0.001). Eighty-three percent of patients had a fall of haemoglobin concentration of 1 g/dl or more, while in 16% of patients the haemoglobin fell greater than or equal to 3 g/dl. Increasing age was found associated with an increased magnitude of dapsone-related haemolysis (P less than or equal to 0.004). Decreasing the daily dose of dapsone was associated with an increased haemoglobin concentration (P less than 0.001%). We have concluded that dapsone commonly results in not only haemolysis but a significant decrease in haemoglobin concentration. This may have serious clinical implications, especially in endemic areas, where, owing to nutrition, malaria, and intestinal parasitism, the haemoglobin concentration is already compromised.

Adolescent↗
PubMed1999

Studies on risk of leprosy relapses in China: relapses after treatment with dapsone monotherapy.

Based upon the data from the Chinese National System for Leprosy Surveillance, this paper reports on the relapses in 297,343 leprosy patients [multibacillary (MB) 106,518, paucibacillary (PB) 190,825] cured by dapsone monotherapy. A total of 11,055 (MB 8675, PB 2380) patients relapsed during an accumulated follow-up period of 4,229,050 patient-years (PY), giving an overall relapse rate of 3.72 per 100 cases or 2.61 per 1000 PY, i.e., 8.14% or 5.91 per 1000 PY over an average follow-up period of 13.8 +/- 8.4 years in MB patients and 1.25% or 0.86 per 1000 PY over an average period of 14.5 +/- 8.9 years in PB patients. For either the overall relapse rate per 100 cases or per 1000 PY, the differences between MB and PB patients were statistically significant, except during 36-40 years of follow up. For both MB and PB patients, the relapse rates showed consistently significant decreases year by year, particularly in PB patients whose relapse rate per 1000 PY was 1.21 in year 10 of follow up; whereas it remained more than 10 per 1000 PY in MB patients. In view of that, the overall relapse rates in MB and PB patients cured by dapsone monotherapy were acceptably low, and most of these patients have been followed up for more than a mean incubation period of observed dapsone relapse. Along with the further extension of follow up, the risk of relapse in dapsone-cured patients will not be expected to increase. This conclusion should be considered when planning policy for the management of patients released from dapsone monotherapy.

China↗
PubMed2000

Pharmacokinetic profiles in rats after intravenous, oral, or dermal administration of dapsone.

Dapsone is a potent anti-inflammatory and antibacterial agent that has been used extensively in the oral treatment of leprosy and dermatitis herpetiformis. This study compared the pharmacokinetic profile of dapsone in rats given a single oral or i.v. 12 mg/kg dose (n = 8/group) or a single dermal application of 12 or 60 mg/kg (n = 12/group) in an aqueous gel application medium containing 10 or 25% diethylene glycol monoethyl ether (DGME). Blood samples (200 microl) were collected via tail vein from each rat and pooled at intervals up to the 24-h period. A terminal blood sample was collected by cardiac puncture from each animal. Plasma concentrations of dapsone were determined by liquid chromatography atmospheric pressure ionization tandem mass spectroscopy. There was no treatment-related overt toxicity observed in any of the animals. Peak levels were reached 1 h after oral dosing (4890 ng/ml), and 6 to 8 h after dermal application, with Cmax values of 1.62, 5.56, and 12.8 ng/ml, for 12 mg/kg at 10 or 25% DGME, and for 60 mg/kg at 25% DGME, respectively. Bioavailability was calculated at 78% after oral dosing and <1% after dermal application. Apparent elimination half-lives (t(1/2))s were similar after i.v. and oral dosing. Both the calculated area under the plasma concentration versus time curve up to 24 h and Cmax values were 3- to 4-fold higher in the dermal application group administered 12 mg/kg dapsone in 25 versus 10% DGME gel, whereas the calculated area under the plasma concentration versus time curve up to 24 h and Cmax values for the 60 mg/kg group were only 3.3- and 2.3-fold greater than those obtained after application of 12 mg/kg in 25% DGME. These results show that both systemic exposure and peak plasma concentrations of dapsone are minimized by dermal versus oral administration of the compound.

Administration, Cutaneous↗
PubMed1992

Dapsone-induced methemoglobinemia and hemolytic anemia.

The treatment of two common adverse effects of dapsone (methemoglobinemia and hemolytic anemia) is discussed, and a case of acute dapsone intoxication is described. A pregnant 29-year-old woman was admitted to an emergency room three hours after ingesting 50 tablets of dapsone (100 mg each) and six alcoholic drinks. One hour after admission 50 g of activated charcoal was given p.o., and 65 mg of methylene blue was given i.v. The patient was found to have a methemoglobin concentration of 25.1%. Arterial blood gases while the patient was breathing 4 L/min of oxygen by nasal cannula were PO2, 136 mm Hg (72.1% saturation); PCO2, 28.9 mm Hg; bicarbonate content, 18.9 mmol/L; and pH, 7.42. Oxygen therapy was changed to 100% oxygen by face mask, 50 g of activated charcoal in sorbitol was administered p.o., and another 65 mg of methylene blue was given i.v. Two more 50-g doses of activated charcoal in sorbitol were given (18.5 and 22 hours after dapsone ingestion). Methylene blue 130 mg was given 14 hours after dapsone ingestion, and 65 mg was given 21, 36, and 55.5 hours after ingestion. Methemoglobin concentrations never rose above 20% after the sixth dose of methylene blue. On hospital days 2 and 3, laboratory values were consistent with a diagnosis of hemolytic anemia; the patient received two units of packed red blood cells. The hematocrit decreased over the next three days to 23.9%, and the patient received four units of packed red blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Treatment of bullous pemphigoid with dapsone, methylprednisolone, and topical clobetasol propionate: a retrospective study of 62 cases.

Dapsone has been used successfully as adjuvant therapy for bullous pemphigoid (BP). The effectiveness of dapsone for this indication, however, remains controversial. We evaluated the effectiveness and adverse events of dapsone (1.0-1.5 mg/kg per day) in combination with oral methylprednisolone (tapering doses of 0.5 mg/kg per day) and topical clobetasol propionate (initially applied once daily on lesions only) in the treatment of BP. Sixty-two patients treated with this regimen were analyzed retrospectively. Patients were free of new blisters after a mean (+/- SD) of 22 +/- 13 days (median, 20 days). After 3 and 6 months of treatment, methylprednisolone could be reduced to less than 10 mg/d in 71% and 91% of patients, respectively; after 12 months of treatment, 53% of patients were in complete remission without receiving further therapy. Dapsone-related side effects were usually mild except in 3 patients (5%), 2 patients with anemia (hemoglobin level, <7 g/dL) and 1 with agranulocytosis. Our data suggest that dapsone used in combination with systemic and topical corticosteroids may be a relatively safe and effective treatment option for BP.

Administration, Oral↗
PubMed1991

Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii pneumonia.

In a prospective, noncomparative study, seven patients with mild Pneumocystis carinii pneumonia, characterized by room air arterial PO2 greater than 60 mm Hg at the time of presentation, were treated with dapsone alone at a dose of 200 mg daily. Two of the seven patients required mechanical ventilation for respiratory failure on day 5 of dapsone therapy; both died. Four patients experienced major side effects during dapsone therapy. None of the seven patients successfully completed a full course of therapy with dapsone. We conclude that high-dose, single-agent dapsone is not suitable for further study as therapy for Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Investigations into the haemolytic effects of dapsone therapy in leprosy patients.

Investigations into the haemolytic effects of dapsone therapy were carried out in forty four leprosy patients admitted to the Sacred Heart Leprosy Centre, Kumbakonam. They received weight based dapsone dosages varying from 1.3-3.3 mg/kg body weight. Blood levels and urinary Dapsone/creatinine ratio were assessed at 1 day, 7 days and 30 days of Dapsone treatment. At the same points of time, haematological observations were also carried out. Serum bilirubin as well as blood mathaemoglobin were also examined. The findings showed a reduction in Hb levels at 30 days observation in a good proportion of cases on 100 mg. In one case (child) weighing 15 kg and receiving 50 mg dapsone increased mathaemoglobin was observed. It is suggested that dapsone dosage be regulated to body weight and preferably not to exceed 1.5 mg/kg body weight.

Adolescent↗
PubMed1988

Secondary and primary dapsone resistant leprosy: an analysis of 199 patients from St. Thomas Hospital and leprosy project, Chettupattu, South India.

The occurrence of secondary and primary dapsone resistance in 199 patients in our control area and the influence of certain variables such as age, initial bacteriological and morphological indices, duration of regular dapsone monotherapy, on the emergence of dapsone resistance was investigated. Ninety one of 122 patients and 29 out of 77 showed secondary (SDR) and primary (PDR) resistance to dapsone respectively. Very low BI (BI:2.5) group also showed both SDR (60%) and PDR (40%). Low or high MI group exhibited the same degree of resistance. Multiplication of M. leprae was obtained even when the MI of the inocula was zero. Even in the group who had 1 to 5 years duration of regular dapsone treatment, 85% patients showed SDR. Significance of such results are discussed in relation to chemotherapy. The overall minimum prevalence of SDR was found to be 5.6% and 21% in the case of PDR in our control area.

Age Factors↗
PubMed1985

Dapsone resistant leprosy, the western Kenya experience.

41 patients out of 804 registered lepromatous (LL) and borderline lepromatous (BL) patients were studied for possible dapsone resistance by series of biopsy specimens, skin smears and clinical examination. These patients were drawn from a pool of 4384 registered leprosy patients in the west Kenya Leprosy Control Project area. Six out of fourty one cases (14.6%) were confirmed as dapsone resistant by series of biopsy specimens taken when patients were on supervised dapsone therapy; 11 patients (26.8%) were suspected to be resistant and 24 patients (58.6%) responded well to dapsone therapy. All the confirmed cases were lepromatous leprosy cases. We therefore found that there is dapsone resistance here with a maximal prevalence rate of 7 per 1000 in all lepromatous cases and 14.6% in clinically suspicious cases.

Dapsone↗
PubMed1977

A comparison of low and conventional dosages of dapsone in the treatment of lepromatous leprosy.

A therapeutic trial using two dosages of Dapsone with a schedule of administration of the drug once a week was undertaken at the Central Leprosy Teaching and Research Institute, Chingleput. Adult males with active lepromatous leprosy who were either previously untreated, or who had no specific treatment for at least three months immediately prior to their inclusion into this study, were the subjects of this trial. Two dosages, viz., 10 mg. per kg. body weight/week, and 3.3 mg. per kg. body weight/week, were employed in this trial. It was found that Dapsone administered orally as a single dose once a week was therapeutically effective in most of the patients, and improvement, clinical or bacteriological, was directly related to the duration of treatment, irrespective of the dosage of Dapsone. Blood levels of Dapsone in these patients were in general commensurate with the dose of the drug in either group. No adverse effects on any of the visceral functions were encountered during the prolonged use of this schedule of treatment with Dapsone.

Dapsone↗
PubMed1982

Intramuscular injection of dapsone in therapy for leprosy: a new approach.

Dapsone is the drug of first choice in the treatment of leprosy. Although the oral route of administration has been mostly used, recent studies of patient compliance revealed that only about 50% of the tables received by the patients are actually taken. It is generally assumed that irregular self-medication favors the development of dapsone resistance. The need for a more reliable route of administration led us to investigate the possibility of an i.m. dapsone depot injection. To achieve effective blood levels for 3-4 weeks, suspensions of large dapsone particles in an aqueous vehicle were made. In a trial with 20 leprosy patients in Nigeria, injection of 900 mg dapsone i.m. as a mixture of particle sizes less than 90 micrometer (20%) and 90-125 micrometer (80%) resulted in a serum level above 0.5 microgram/ml for 18 +/- 5 days with a mean peak concentration of 3.1 +/- 0.9 microgram/ml (n = 10). Injection of 1200 mg of the same particle-size mixture led to peak concentrations of 2.7 +/- 1.0 microgram/ml and maintenance of the level above 0.5 microgram/ml for 25 +/- 3 days (n = 5). After injection of 1200 mg (particle size less than 90 micrometer), serum levels were kept above 0.5 microgram/ml for 21 +/- 5 days with a maximum concentration of 3.9 +/- 1.2 microgram/ml (n = 5). Serum levels were measured using a rapid non-extractive HPLC method. The injections were very well tolerated. Due to these encouraging results, the dosage and formulation will be further optimized.

Adult↗
PubMed1982

Monitoring the regularity of self administration of dapsone by leprosy patients.

An operational study was undertaken (1) to monitor and assess the regularity of DDS intake by leprosy patients, (2) to find out the operational feasibility of methods used for monitoring dapsone intake, and (3) to study the factors influencing the regularity of drug intake. The self administration of Dapsone by 319 leprosy patients, attending 6 field clinics of our Mobile Treatment Unit was assessed by (1) Physical verification of Dapsone tablets and (2) screening their urine for DDS by spot test (in the field itself) and by estimating DDS/Cr. ratio in urine (in Biochemistry Lab.). As assessed by physical verification of Dapsone tablets, on an average one patient has missed 3.67 +/- 3.96 tablets in a fortnight, and only 62% patient took more than 75% of treatment. The spot test was found to be positive in 84.64% of the patients. Both the methods of monitoring the regularity of dapsone intake were found operationally very feasible and acceptable and had a good correlation with each other. The spot test was found very reliable as judged by DDS/Cr. ratio. Both the methods can be used on a mass scale in National Leprosy Control Programme for the purpose.

Adolescent↗
PubMed1980

Prevalence of secondary dapsone resistance in Gudiyattam Taluk, the leprosy control area of the Schieffelin Leprosy Research and Training Centre, Karigiri. 1. Preliminary report.

A preliminary study of the prevalence rate of secondary dapsone resistance among leprosy patients in Gudiyattam Taluk, Tamil Nadu, was undertaken. During the period March 1978 to February 1979, there were 1580 lepromatous and borderline lepromatous patients considered to be at risk of developing secondary resistance. Of them, 1431 were examined clinically, and reactivation and/or relapse was found in 114 patients. Of these, 46 had a bacteriological index of 2,000 and more. Skin biopsies were taken from 26 patients for mouse foot pad studies. Resistance to dapsone at the highest drug concentration was found in 22 and partial resistance in two patients. The organisms from two patients were sensitive to dapsone. Twenty patients were not biopsied because they had been absent from treatment for significant periods of time. These patients are now under observation. Prior to this study, nine patients had been confirmed to have dapsone resistance in the control area, and during the present study 24 additional patients with secondary resistance have so far been detected. Thus 33 patients with dapsone resistance among the 1431 patients examined yields a crude prevalence rate of 2.3% in Gudiyattam Taluk.

Dapsone↗
PubMed1993

Clarithromycin is bactericidal against strains of Mycobacterium leprae resistant and susceptible to dapsone and rifampin.

The anti-Mycobacterium leprae activity of clarithromycin when administered alone and in combination with rifampin and dapsone in the diet was determined using the kinetic method of drug evaluation in mice. Clarithromycin when administered at a concentration of 0.1% (w/w) in the diet completely prevented growth of 2 pan-susceptible, 3 dapsone-resistant, 2 rifampin-resistant, and 2 rifampin and dapsone double resistant strains of M. leprae. A 0.03% (w/w) concentration also completely prevented growth of M. leprae in all mice infected with 2 of 7 strains tested, but in only some of the mice infected with the remaining 5 strains. No antagonistic drug interactions were observed between clarithromycin and dapsone or rifampin. The addition of clarithromycin to the currently recommended multidrug regimen should improve the rate of killing of M. leprae and help to prevent the growth of dapsone-resistant and rifampin-resistant strains.

Administration, Oral↗