Drug Interactions between aliskiren and Vilevev MB

ADJUST DOSING INTERVAL: Bowel cleansing products can increase the gastrointestinal transit rate. Oral medications administered within one hour of the start of administration of the bowel cleansing solution may be flushed from the gastrointestinal tract and not properly absorbed.

MANAGEMENT: Patients should be advised that absorption of oral medications may be impaired during bowel cleansing treatment. Oral medications (e.g., anticonvulsants, oral contraceptives, antidiabetic agents, antibiotics) should not be administered during and within one hour of starting bowel cleansing treatment whenever possible. However, if concomitant use cannot be avoided, monitoring for reduced therapeutic effects may be advisable.

GENERALLY AVOID: Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren. The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and/or increased ionization of aliskiren due to reduced intestinal pH. In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water. Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water. No significant differences were observed in the blood pressure or heart rate between treatments. However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose. A similar pharmacokinetic interaction has been reported with grapefruit juice. In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water. A high degree of interpatient variability was observed with all three interactions.

MONITOR: High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren. According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively. In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.

MANAGEMENT: To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals. Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.