Cost-effectiveness of agents used for evaluation of ureteral patency during intraoperative cystoscopy in gynecologic and urogynecologic surgery.

BACKGROUND: Intraoperative evaluation of ureteral patency is often performed in gynecologic and urogynecologic surgery. Many agents are used to help assess the patency, each with its own associated cost, ease of use, and adverse reactions. Some agents, such as dextrose, are used as an instillation fluid to create a viscosity difference and aid the visualization of a ureteral jet. Others, such as oral phenazopyridine or the intravenous use of sodium fluorescein and indigo carmine, cause a color change of the urine to directly aid the visualization of ureteral jets. Recently, numerous studies have examined the efficacy and surgeon satisfaction of these agents. The studies have also emphasized certain options as associated with a lower cost. However, there have not been any cost studies comparing these agents. OBJECTIVE: To compare the cost-effectiveness of the following 4 agents that are commonly used in assessing ureteral patency intraoperatively: oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. STUDY DESIGN: We constructed a decision-analytic model to compare cystoscopy using oral phenazopyridine, dextrose instillation, intravenous sodium fluorescein, and intravenous indigo carmine. Failure to see efflux resulted in work-ups for ureteral obstruction. The probabilities were obtained from published studies, and the probability of successfully seeing efflux ranged from 0.92 with oral phenazopyridine to 0.99 with intravenous indigo carmine. The costs of the agents, adverse effects, and ureteral obstruction work-ups were obtained from the University of North Carolina at Chapel Hill Department of Pharmacy, the Healthcare Cost and Utilization Project 2016 database and the FAIR Health Consumer database. The cost of a ureteral obstruction work-up used in our model ranged from $9755 for intraoperative evaluation with retrograde pyelograms and stents to $29,034 for hospitalization. Our primary outcome was the incremental cost-effectiveness ratio per unnecessary work-up for ureteral obstruction avoided. Sensitivity analyses were performed to identify the key uncertainties. RESULTS: Oral phenazopyridine, followed by an intravenous agent if needed, had a mean cost of $110 per patient. Dextrose averaged $151 more per patient, with only a slight improvement in avoiding unnecessary ureteral obstruction work-ups and a higher cost associated with adverse reactions (incremental cost-effectiveness ratio, $62,000). Intravenous agents cost approximately $1000 more per patient and were less effective at preventing unnecessary work-ups. Sensitivity analyses did not identify any thresholds that would significantly change the outcomes. CONCLUSION: Our model suggests that oral phenazopyridine and dextrose instillation are the least expensive and the most effective agents to aid in the visualization of ureteral patency during intraoperative cystoscopy, although dextrose is associated with higher costs owing to a higher rate of adverse reactions (primarily urinary tract infections). Intravenous sodium fluorescein and indigo carmine are historically popular first-choice agents. However, they were found to be more expensive and less effective as primary agents in our model and should likely be reserved for use as secondary agents in the event that the visualization of ureteral jets is unclear with the initial use of phenazopyridine or dextrose.

The Effect of Phenazopyridine on Immediate Postoperative Voiding After Prolapse Surgery: A Randomized Controlled Trial.

OBJECTIVES: The objective of our study was to determine if phenazopyridine reduces void trial (VT) failure rates after prolapse surgery. METHODS: A single-institution randomized controlled trial was conducted comparing a second dose of phenazopyridine 200 mg on postoperative day 1 versus no additional phenazopyridine in women undergoing prolapse surgery. All subjects (including controls) received 200 mg of phenazopyridine preoperatively for ureteral patency verification. The intervention group received a second dose of phenazopyridine 200 mg the morning of postoperative day 1. The primary outcome was assessed using a standardized VT. Secondary outcomes included pain, opioid usage, urinary tract infections, and prolonged or recurrent urinary retention. An intent-to-treat analysis was performed with a χ2 test to compare failure rates between the intervention and control groups. RESULTS: We enrolled 152 women, and 76 were randomized to each group. There was no difference in VT failures between the 2 groups-34% failed without phenazopyridine on postoperative day 1, and 42% failed with phenazopyridine on postoperative day 1 (P = 0.326). Subject characteristics were similar across both groups. Pain scores immediately before the VT were 3 out of 10 in both groups (P = 0.206), with no difference in opioid consumption (P = 0.750). There were no differences in the rate of urinary tract infections or prolonged or recurrent urinary retention between the groups (P = 0.304 and P = 0.745). CONCLUSIONS: While previous studies suggested an improvement in immediate postoperative voiding with phenazopyridine, our randomized controlled trial does not support this.

Safety analysis of long-term phenazopyridine use for radiation cystitis.

BACKGROUND: Phenazopyridine is a urinary tract analgesic indicated for short-term treatment of irritation in the lower urinary tract. Despite the lack of evidence for extended use, it is often used in varying durations for supportive care for cancer patients with radiation-induced cystitis. The objective of this study was to compare the incidence of adverse drug reactions in patients with radiation cystitis receiving long-term phenazopyridine (>14-day supply) compared to a matched comparator group. METHODS: This retrospective cohort study compared adverse events among cancer patients with and without phenazopyridine exposure. Included patients received radiation and at least one chronic medication between 1 July 2008 and 30 June 2017. The phenazopyridine group also received >14-day supply of phenazopyridine during the study period. Patients were matched based on gender, age (±5 years), cancer diagnosis, and palliative or curative treatment intent. Data collection occurred at baseline, during the time of presumed exposure, and through the end of the study period for surveillance purposes. RESULTS: A total of 272 patients received phenazopyridine for >14-day supply during the study period. Of these, 90 patients were included and matched to an equal number of patients in the comparator group. The included patients were similar between groups and were largely male with a diagnosis of prostate cancer. Most patients received between a 30- and 60-day supply of phenazopyridine. There were a total of 13 adverse drug reactions in the phenazopyridine group and 18 in the comparator group (p = 0.32). No differences were identified between the phenazopyridine and comparator groups for the incidence of individual adverse drug reactions, emergency department visits, hospitalizations, or new diagnoses of hepatocellular or colorectal cancer. CONCLUSION: There was no difference in adverse drug reactions among patients receiving phenazopyridine for >14 days compared to a matched comparator group. The overall incidence of adverse events in both groups was low.

Effectiveness of Assessing Ureteral Patency Using Preoperative Phenazopyridine.

OBJECTIVES: The aims of this study were to determine the efficacy of phenazopyridine when used intraoperatively to assess ureteral patency and to investigate factors that may influence its efficacy. METHODS: This is a retrospective chart review performed at the Olive View-UCLA Medical Center, a Los Angeles County teaching hospital, from January 2014 through July 2016. Patients undergoing cystoscopy at the time of gynecologic surgery were identified via department case logs. All women receiving preoperative oral phenazopyridine were included. If ureteral flow was unable to be visualized with phenazopyridine alone, the medication was deemed ineffective, and sodium fluorescein was given intraoperatively. Patients were divided into a phenazopyridine effective or phenazopyridine ineffective group. Patient demographics, renal function, intraoperative fluids and urine output, estimated blood loss, timing and dose of medication administration, and complications were gathered from the chart and compared between groups using Fisher exact test, 2-sample t test, Wilcoxon test, and logistic regression for multivariable analysis. P < 0.05 was determined to be significant. RESULTS: Preoperative phenazopyridine was effective in 190 (91.8%) of 207 patients. It was ineffective in 17 patients who then required intraoperative sodium fluorescein. The group in which phenazopyridine was effective was more likely to have been given a 200-mg (vs 100-mg) dose (P = 0.02) and had lower intraoperative urine output (median, 450 vs 800 mL; P = 0.002). CONCLUSIONS: Preoperative oral phenazopyridine is effective in more than 90% of cases to detect during gynecologic surgery. A higher phenazopyridine dose and lower intraoperative urine output were associated with increased efficacy.

Phenazopyridine: A Preoperative Way to Identify Ureteral Orifices.

OBJECTIVE: To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange, can be administered orally preoperatively. We evaluated the usefulness of phenazopyridine in identifying the UOs and optimal timing of administration. METHODS: Adult patients undergoing endoscopic procedures at the Stratton VA were prospectively enrolled. Preoperative metabolic panels were reviewed. Exclusion criteria were renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or severe liver disease, glucose-6-phosphate dehydrogenase deficiency, previous hypersensitivity to phenazopyridine, or pregnancy. In phase 1, patients undergoing office flexible cystoscopy were administered 200 mg phenazopyridine the morning of the procedure. Because of the robust orange color of the urine, phase 2 was implemented. In phase 2, patients undergoing rigid cystoscopy in the operating room took 200 mg phenazopyridine at 7 PM the night before surgery. Upon entry into the bladder, UOs were identified and urine color was graded (0 = no dye, 1 = weak, 2 = moderate, and 3 = strong). Patients were assessed postoperatively for side effects. RESULTS: Five patients were included in phase 1. The mean time from medication to cystoscopy was 153 minutes (range 17-304 minutes). One-third of patients had excretion of grade 3 orange urine that obscured inspection of the bladder mucosa. The study design was adjusted and we transitioned to phase 2. Twenty-three patients were enrolled in phase 2. The mean time from phenazopyridine dose to cystoscopy was 14 hours (range 13-17 hours). Seventy-three percent of patients had grade 2 efflux from the UOs. CONCLUSION: Phenazopyridine can successfully identify UOs and can be administered as early as the evening before the procedure.

The Effect of Oral Phenazopyridine on Perioperative Voiding After Midurethral Slings (EPIPhANy Study).

OBJECTIVE: To determine the effect of preoperative oral phenazopyridine on postoperative voiding dysfunction in women undergoing a retropubic midurethral sling. METHODS: A single-institution randomized clinical trial was performed from September 2015 to March 2017, comparing 200 mg of oral phenazopyridine versus no phenazopyridine in patients undergoing a retropubic midurethral sling under general anesthesia with no concomitant procedures. A power calculation indicated that we required at least 40 subjects per arm. Preoperative demographics, intraoperative medications, blood loss, and complications were recorded. A standardized voiding trial was performed before discharge. Voiding dysfunction was determined by the proportion of subjects who failed a postoperative voiding trial. Pain scores were obtained before and 2 to 3 hours after the surgical procedure. Patient characteristics and surgical data were compared using χ, Fisher exact test, or Wilcoxon rank sum test. RESULTS: Ninety-two subjects were enrolled in the study. Three patients cancelled their surgery and 1 had an intraoperative urethral injury, leaving 88 patients for the final analysis (44 per arm). Patient demographics showed no differences between groups. Phenazopyridine did not reduce the proportion of patients who failed the voiding trial (27%) compared with subjects who did not receive the medication (21%) (P = 0.453). Postoperative visual analog pain scores were higher in those not receiving phenazopyridine (1.76 vs 1.21, P = 0.046), but after adjusting for the difference in preoperative and postoperative pain scores, the groups showed no difference (P = 0.087). CONCLUSIONS: Our prospective trial shows that phenazopyridine has no effect on short-term postoperative voiding dysfunction. This condition appears to be multifactorial, and further research is needed.

The Effect of Preoperative Phenazopyridine on Urinary Retention Following Midurethral Sling.

OBJECTIVE: The aim of this study was to determine the effect of preoperative oral phenazopyridine on short-term voiding dysfunction in patients undergoing a retropubic midurethral sling. METHODS: We conducted a retrospective cohort study in subjects undergoing a retropubic midurethral sling comparing those who received preoperative oral phenazopyridine with those who did not. We included all women who underwent a retropubic midurethral sling without concomitant procedures under general anesthesia at our institution. Slings were placed by either suprapubic or transvaginal approach, per surgeon's preference. Demographics and intraoperative data on preoperative dose of phenazopyridine and medications linked to voiding dysfunction were captured. RESULTS: One hundred seventy-four subjects were identified. Twenty-five subjects failed to meet inclusion and exclusion criteria and were excluded, and 149 subjects comprised the final groups. Eighty-two subjects (55.03%) received phenazopyridine, and 67 (44.97%) did not. Most subjects received a 200-mg dose (97.6%). Except for surgical approach, both groups receiving and not receiving phenazopyridine had similar demographic characteristics. Eighty-eight percent of the subjects who received phenazopyridine passed the voiding trial versus 73.1% (odds ratio, 2.98; 95% confidence interval, 1.23-7.17). After adjusting for medications, estimated blood loss, number of trocar passages, or bladder perforation, the patients receiving phenazopyridine were still more likely to pass the postoperative voiding trials compared with those who did not (odds ratio, 2.97; 95% confidence interval, 1.10-7.98). CONCLUSIONS: Our findings suggest that the preoperative administration of phenazopyridine may improve postoperative voiding function after a retropubic midurethral sling. Additional prospective trials are needed to confirm this finding.

Comparison of Times to Ureteral Efflux after Administration of Sodium Fluorescein and Phenazopyridine.

PURPOSE: There is currently a national shortage of indigo carmine. In efforts to identify the most efficient aid for visualizing ureteral efflux intraoperatively we investigated the time to excretion of phenazopyridine vs a newly identified alternative, sodium fluorescein. MATERIALS AND METHODS: We analyzed prospectively collected data on a cohort of women who underwent pelvic reconstructive surgery in 2015. Per provider preference patterns a number of patients were administered 200 mg phenazopyridine orally with a sip of water 1 hour prior to the start of operative time. Other patients were given 0.5 ml 10% sodium fluorescein intravenously in the operating room. In all cases time was measured between the administration of the agent and the visualization of color changes consistent with agent efflux in an indwelling catheter, which was placed at the start of the operation. Differences in excretion times between the groups were compared with the Wilcoxon rank sum test. RESULTS: Seven women received phenazopyridine and 5 received sodium fluorescein. Mean excretion time was significantly longer in the phenazopyridine group compared to the sodium fluorescein group (81.9 vs 5.1 minutes, p = 0.0057). Median excretion time for phenazopyridine was 70 minutes (range 59 to 127) and for sodium fluorescein it was 5 minutes (range 3 to 9). CONCLUSIONS: Sodium fluorescein is excreted significantly faster in the operating room compared to phenazopyridine. Depending on the cost of these agents at an institution, in addition to the desire to decrease operative time, this may impact practice patterns and agent selection.

Intraoperative Cystoscopic Evaluation of Ureteral Patency: A Randomized Controlled Trial.

OBJECTIVE: To compare different modalities to aid in the evaluation of intraoperative ureteral patency on cystoscopy in the postindigo carmine era. METHODS: In a randomized controlled trial, participants undergoing pelvic surgery were randomized into one of four groups: saline distention (control), 10% dextrose distention, oral phenazopyridine, or intravenous sodium fluorescein. Our primary outcome was visibility of the ureteral jets. Secondary outcomes included surgeon satisfaction; adverse reactions including allergies, urinary tract infections, urinary retention, cystoscopy times, and ureteral obstruction; and delayed diagnosis. Participants were followed for 6 weeks. A sample size of 176 participants was planned to demonstrate a 30% difference in the visibility scale. All analyses were performed in an intention-to-treat fashion. RESULTS: From February 25, 2015, through August 2015, 176 participants were enrolled; 174 completed the trial, and two did not undergo intervention. Forty-four participants were included in the phenazopyridine, dextrose, saline, and sodium fluorescein groups. Sodium fluorescein and 10% dextrose resulted in significantly improved visibility and satisfaction when compared with the control group (P<.001 and P=.004, respectively). Dextrose provided the highest satisfaction and phenazopyridine provided lowest, but visibility was not statistically different between the two groups (P=.101). Three ureteral obstructions were identified intraoperatively and none in the postoperative period. Mean total cystoscopy time varied between 4.0 and 4.8 minutes and postoperative urinary retention rate was 50% across all groups. Overall urinary tract infection rate was 24.1%, which was similar between interventions. There were no related adverse events. CONCLUSION: Compared with the control, 10% dextrose and sodium fluorescein resulted in improved visibility and provided significantly more satisfaction in the evaluation for ureteral patency with no considerable increase in operative time or morbidity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02476448.

The association of antimicrobial resistance with cure and quality of life among women with acute uncomplicated cystitis.

BACKGROUND: The association of in vitro resistance with bacteriologic, clinical, and health-related quality of life (HRQoL) outcomes for acute uncomplicated cystitis is unclear. METHODS: We conducted a prospective study of women aged 18-40 years with acute uncomplicated cystitis symptoms for ≤7 days who subsequently grew an Enterobacteriaceae sp. and initially received trimethoprim/sulfamethoxazole (TMP/SMX) and phenazopyridine. We conducted telephone follow-up evaluating clinical cure at 1-3 days and in-person follow-up evaluating clinical, bacteriologic, and HRQoL outcomes at 3-7 days and 4-6 weeks post-treatment. RESULTS: An Enterobacteriaceae sp. was isolated in 139 (96.5%) patients (25.2% TMP/SMX-resistant). At 1-3 days post-treatment, clinical cure occurred in 56/81 (69.1%) and 14/31 (45.2%) of cases with susceptible and resistant strains, respectively (difference 23.9%; 95% confidence interval [CI], 1.5-46.4%). At 3-7 days post-treatment, bacteriologic cure occurred in 70/73 (95.9%) and 15/25 (60%) of cases with susceptible and resistant strains, respectively (difference 35.9%; 95% CI, 13.5-58.3%). Sustained clinical cure rates at 3-7 days and 4-6 weeks post-treatment were 65.4 and 56.8% with susceptible strains, and 45.2 and 45.2% with resistant strains, respectively. The HRQoL scale assessing role limitations due to physical health problems was lower in TMP/SMX-resistant versus TMP/SMX-susceptible infections, with twice as many hours of missed activities reported (mean, 18.4 vs. 9.1 h). Differences in HRQoL appeared to be largely related to differences in clinical cure rates. CONCLUSIONS: Among women treated for acute uncomplicated cystitis with TMP/SMX, in vitro TMP/SMX resistance was associated with lower bacteriologic and clinical cure rates, and had greater impact on the time lost from daily activities compared to those with TMP/SMX-susceptible infections.

Ciprofloxacin bioavailability is enhanced by oral co-administration with phenazopyridine: a pharmacokinetic study in a Mexican population.

BACKGROUND: and objective: In Mexico, urinary tract infections (UTIs) constitute the second most frequent type of infections treated at primary-care clinics. Ciprofloxacin has played a major role in the treatment of UTIs because it has a broad spectrum of antibacterial activity. In addition to antimicrobial agents, phenazopyridine has been used to alleviate symptoms that occur during episodes of UTI. Thus, the present study was designed to compare the pharmacokinetic behaviour of ciprofloxacin administered alone versus ciprofloxacin combined with phenazopyridine. PATIENTS AND METHODS: Twenty-four healthy male Mexican volunteers participated in this project. The study was carried out with a single oral dose of ciprofloxacin 500mg. The double-blind, crossover, randomised, balanced trial design comprised two treatments, two periods and two sequences. After administration of the study medication, serial blood samples were collected for a period of 12 hours. The harvested plasma was analysed for ciprofloxacin by high-performance liquid chromatography. The area under the concentration-time curve to last measurable concentration (AUC(t)), area under the concentration-time curve extrapolated to infinity (AUC(infinity)), peak plasma concentration (C(max)), time to reach C(max) (t(max)), mean residence time (MRT), elimination constant (k(e)) and elimination half-life (t(1/2)) were determined from plasma concentrations of both treatments and considered as primary variables for statistical analysis. RESULTS: While there were no differences between the two treatments in terms of C(max) and k(e), AUC(t )and AUC(infinity) were 35% and 29% higher, respectively, in the combined treatment arm. Moreover, a significant delay in t(max )(from 1 to 1.5 hours) and a statistical increase of 29% in MRT were also observed with phenazopyridine co-administration. CONCLUSION: Oral co-administration of phenazopyridine increases ciprofloxacin bioavailability with regard to the amount absorbed (AUC) and permanence in the body (MRT), which could be useful during treatment.

Phenazopyridine-induced sulfhemoglobinemia.

OBJECTIVE: To report a case of sulfhemoglobinemia in a patient receiving phenazopyridine for a urinary tract infection. CASE SUMMARY: A 63-year-old white woman presented to the emergency department with complaints of fatigue and bluish discoloration of her body that had gradually progressed over the previous 6-8 weeks. About 4 months prior to presenting to the emergency department, she had started taking phenazopyridine, an over-the-counter medication for symptoms of dysuria. Because the cyanosis did not improve after the patient received oxygen and methylene blue, sulfhemoglobinemia was suspected and confirmed by spectrophotometer analysis. DISCUSSION: Sulfhemoglobin is a green-pigmented molecule containing a sulfur atom in one or more of the porphyrin rings. It is a rare cause of cyanosis, which is usually drug induced. Sulfhemoglobinemia is suspected when a cyanotic patient has normal to near-normal oxygen tension, laboratory reports of elevated methemoglobin, and does not respond to methylene blue therapy. Sulfhemoglobinemia is relatively rare, despite the widespread use of drugs that have been reported to cause it. Predisposing factors, such as chronic constipation, present in our patient, have been suggested as a source of hydrogen sulfide. CONCLUSIONS: This case of sulfhemoglobinemia, which occurred after the patient took phenazopyridine, is considered a probable adverse event according to the Naranjo probability scale.

Phenazopyridine in the management of autonomic dysreflexia associated with urinary tract infection.

OBJECTIVE: Documentation of possible usefulness of phenazopyridine in the management of autonomic dysreflexia (AD) associated with urinary tract infection. SETTING: Veterans Administration Spinal Cord Injury Center. RESULTS: A 36-year-old man with tetraplegia and AD triggered by cystitis improved both subjectively and objectively following the institution of a 2-day course of phenazopyridine. CONCLUSION: Phenazopyridine may be useful in the management of AD associated with cystitis.

Life-threatening Pyridium Plus intoxication: a case report.

A 16-month-old male presents with an overdose of Pyridium Plus, a combination anticholinergic, azo dye, and barbiturate, resulting in seizures, coma, and methemoglobinemia. This case report reviews the treatment of methemoglobinemia with methylene blue, activated charcoal, and exchange transfusion. Additionally, the role of the pulse oximeter is addressed when methemoglobinemia exists and is treated with methylene blue.

Acquired methemoglobinemia from multiple oxidants.

Phenazopyridine has been associated with methemoglobinemia in patients who have received an overdose, have decreased renal function, or are discovered to be unusually susceptible to the drug (ie, they may have an undetected NADH methemoglobin reductase deficiency). The case we have presented is unusual in that normal doses of phenazopyridine were given, no renal dysfunction was evident, and our patient had previously been given this drug without complication. Methemoglobinemia appeared to be the result of metabolic overload by multiple oxidants (phenazopyridine and lidocaine) of the normal reductase pathways in the erythrocytes. We saw no evidence to indicate that bupivacaine contributed to its development. Enzyme pathway changes induced by chemotherapy should be considered, though few studies have linked alterations of enzyme levels and pathways with chemotherapy and malignancy.

The Pyridium pad test for diagnosing urinary incontinence. A comparative study of asymptomatic and incontinent women.

Eighteen women with urodynamically proven genuine stress incontinence awaiting surgery and 23 normal, asymptomatic, continent female volunteers took part in a study to compare the accuracy of a qualitative pad test with a quantitative pad-weighing test in detecting urine loss. Each woman took 600 mg of phenazopyridine hydrochloride (Pyridium, Parke-Davis) in three equally divided doses over 18-24 hours and then underwent a standardized, one-hour pad test as described by the International Continence Society. The Pyridium pad test was regarded as positive if there was any orange staining on the pad. The quantitative pad-weighing test was considered positive if there was a weight gain of 1.0 g or more at the end of the one-hour test period. All 18 patients with genuine stress incontinence had positive Pyridium pad tests, and all had pad weight gains of greater than or equal to 1.0 g (mean, 16.5). The maximum pad weight gain in the asymptomatic, continent volunteers was 0.7 g (mean, 0.1), and none was aware of any urinary leakage during the test; however, 12 (52%) had positive Pyridium pad tests. The Pyridium pad test appears 100% sensitive in detecting urine loss in symptomatic women with genuine stress incontinence, but it has a high false-positive rate in healthy, asymptomatic, continent women. If pad-weighing tests are done, the addition of Pyridium generally will not be useful, and if Pyridium is used by itself, the results may be misleading.

Heinz-body hemolytic anemia associated with phenazopyridine and sulfonamide.

A 27-year-old white woman developed Heinz-body hemolytic anemia following multiple courses of oral phenazopyridine and trimethoprim-sulfamethoxazole. Her diagnosis was supported by the finding of bite cells on peripheral blood smear. The patient's rapid recovery and reversal of abnormal laboratory parameters were consistent with an acquired hemolytic disorder. This case should sensitize the clinician to the development of drug-induced oxidative hemolysis, its clinical features, and its reversibility. It is also important that the clinician recognize those drugs capable of causing this disorder and appreciate the methods available to establish the diagnosis.

Effect of some additives on the properties of phenazopyridine hydrochloride granules and their corresponding tablets.

The effect of the diluents, lactose and calcium carbonate and of the binders, syrup, gelatin, methylcellulose and Eudragit E on the physical properties of phenazopyridine hydrochloride (PNHCl) granules was evaluated. A correlation existed between the granules' physical properties and those of their compressed tablets. With regard to drug release, lactose-syrup 30% was the best of all diluent-binder combinations, followed by lactose-methylcellulose 4%. Also lactose was found to be superior to calcium carbonate in drug release when gelatin and methylcellulose were used as binders. Eudragit E was the best binder with calcium carbonate in this respect. On the other hand, the bioavailability of PNHCl in humans was the same when lactose was used with either gelatin, syrup or methylcellulose, but higher than that obtained with a combination of calcium carbonate and Eudragit E 15%.