Drug interactions between Inderide and Urogesic Blue

hydrochlorothiazide ↔ sodium biphosphate

Applies to:Inderide (hydrochlorothiazide/propranolol) and Urogesic Blue (hyoscyamine/methenamine/methylene blue/sodium biphosphate)

MONITOR CLOSELY: Coadministration with agents that affect renal function or perfusion such as diuretics, ACE inhibitors, angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of acute phosphate nephropathy associated with the use of bowel-cleansing phosphate solutions. The risk and/or severity of fluid and electrolyte disturbances may also be increased, which can lead to serious adverse events including cardiac arrhythmias, seizures, and renal impairment. Acute phosphate nephropathy is a rare adverse event that presents as acute renal failure with minimal proteinuria and a bland urine sediment. Renal biopsy findings are consistent with nephrocalcinosis and include acute and/or chronic renal tubular injury, calcium-phosphate crystal deposition in the distal tubules and collecting ducts, and no other pattern of histological injury. The risk of acute phosphate nephropathy stems from the large phosphate load, fluid shifts, and decreased intravascular volume, which can be exacerbated in the presence of medications that affect renal perfusion or function. In reported cases, acute renal failure was typically diagnosed within two to five months of colonoscopy. These cases often resulted in permanent impairment of renal function, some requiring long-term dialysis.

MANAGEMENT: Caution is advised when bowel-cleansing phosphate preparations are prescribed in patients treated with agents that affect renal function or perfusion, particularly if they are frail or elderly. Bowel-cleansing phosphate preparations should not be used in patients who have impaired renal function or perfusion, dehydration, or uncorrected electrolyte abnormalities. In patients at risk for acute phosphate nephropathy, baseline and postprocedure labs including serum electrolytes, calcium, phosphate, BUN, and creatinine should be performed. Patients should be advised not to exceed the recommended dosage of their bowel-cleansing preparation and to drink sufficient quantities of clear fluids during before, during, and after bowel cleansing. Limited data suggest that administration of an electrolyte rehydration solution may attenuate the electrolyte abnormalities and hypovolemia. Hospitalization and intravenous fluid hydration may be appropriate for frail or elderly patients who may be unable to drink an adequate volume of fluid.

methenamine ↔ hydrochlorothiazide

Applies to:Urogesic Blue (hyoscyamine/methenamine/methylene blue/sodium biphosphate) and Inderide (hydrochlorothiazide/propranolol)

GENERALLY AVOID: Agents that produce an alkaline urine may decrease the antibacterial effectiveness of methenamine. Methenamine is most effective in an acidic milieu (pH less than 5.5) because acidic urine allows the formation of formaldehyde from methenamine. Large doses of antacids may also alkalinize the urine.

MANAGEMENT: This combination should be avoided, if possible. Frequent urine pH testing is recommended.

propranolol ↔ hyoscyamine

Applies to:Inderide (hydrochlorothiazide/propranolol) and Urogesic Blue (hyoscyamine/methenamine/methylene blue/sodium biphosphate)

MONITOR: Anticholinergic agents frequently cause drowsiness and other central nervous system-depressant effects that may be additive with those induced by beta blockers. In addition, these agents may increase heart rate and theoretically may counteract the bradycardic effects of beta blockers. Pharmacokinetically, anticholinergic agents may delay the gastrointestinal absorption of beta blockers and other drugs that are administered orally. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents. In healthy volunteers, pretreatment with propantheline has been shown to prolong the time to reach peak plasma concentration (Tmax) for both atenolol and metoprolol. Propantheline also decreased metoprolol peak plasma concentration (Cmax) but had no effect on its systemic exposure (AUC). In contrast, propantheline increased atenolol AUC but had no effect on its Cmax. The clinical relevance of these changes is probably minimal.

MANAGEMENT: Patients should be monitored for potentially excessive CNS adverse effects (e.g., drowsiness, dizziness, lightheadedness, confusion, blurred vision) if anticholinergic agents are used in combination with beta blockers. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

hydrochlorothiazide ↔ hyoscyamine

Applies to:Inderide (hydrochlorothiazide/propranolol) and Urogesic Blue (hyoscyamine/methenamine/methylene blue/sodium biphosphate)

Anticholinergic agents may increase the absorption and oral bioavailability of thiazide diuretics. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents. In six healthy volunteers, pretreatment with propantheline prolonged the time to reach peak plasma concentration (Tmax) for hydrochlorothiazide from 2.4 to 4.8 hours and increased its total 48-hour urinary recovery by 36%. Similar results were reported for chlorothiazide in another study. The clinical significance of these changes is unknown.