Drug Interactions between nintedanib and Vilevev MB

MONITOR CLOSELY: The following interaction applies only to products containing sodium biphosphate that are used for bowel cleansing. It does not apply to products containing sodium biphosphate that are used for other, non-laxative related purposes.

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.

MONITOR: Coadministration of corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of gastrointestinal (GI) perforation that can occasionally occur with the use of nintedanib. Overall, premarketing clinical data reveal no increased risk of GI perforation in nintedanib-treated patients. There were no reports of GI perforation in patients receiving nintedanib in the phase III clinical studies cited by the prescribing information for the treatment of systemic sclerosis-associated interstitial lung disease and chronic fibrosing interstitial lung diseases with a progressive phenotype. GI perforation occurred in 0.3% of patients (2 cases, both serious) receiving nintedanib compared to 0 cases in placebo-treated patients in the clinical studies for idiopathic pulmonary fibrosis. In the phase III LUME-Lung1 study comparing treatment with nintedanib plus docetaxel against placebo plus docetaxel in patients with locally advanced, metastatic, or recurrent non-small cell lung cancer after first-line chemotherapy, the frequency of GI perforation was comparable between the treatment arms. However, cases of GI perforation and ischemic colitis, including some with fatal outcome, have been reported in the postmarketing period. Although a definitive causal relationship to nintedanib has not been established, the association is possible based on nintedanib's mechanism of action. Additional risk factors for GI perforation include recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease.

MANAGEMENT: Caution is recommended when using nintedanib in combination with other drugs associated with an increased risk of GI perforation, such as corticosteroids and NSAIDs, and in patients with other risk factors such as recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease. Nintedanib should only be used if the anticipated benefit outweighs the potential risk. Some authorities recommend waiting at least 4 weeks after abdominal surgery before initiating nintedanib. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting. Therapy with nintedanib should be permanently discontinued in patients who develop GI perforation.