Drug Interactions between pemigatinib and silodosin

Pemigatinib may be taken with or without food. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with pemigatinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of pemigatinib. This may increase the frequency and severity of serious side effects such as elevated phosphate levels in the blood (which can eventually lead to low blood calcium levels; calcium deposits in the skin, muscles, and other tissues; anemia; muscle cramps; seizures; and irregular heart rhythm), eye and vision problems, joint pain, mouth sores and inflammation, hair loss, diarrhea, nausea, vomiting, and constipation. Talk to your doctor if you have any questions or concerns. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Taking silodosin with food can reduce the risk and/or severity of side effects. Therefore, silodosin should be administered with or immediately after a meal.

The use of silodosin is contraindicated in patients with severe hepatic impairment. No dosage adjustment is needed in patients with mild or moderate hepatic impairment.

The use of silodosin is contraindicated in patients with severe renal impairment (CrCl < 30 mL/min). Caution and regular monitoring is recommended in patients with moderate renal impairment as the plasma concentrations can increase three times higher when compared with subjects with normal renal function. Dose should be reduced to 4 mg/day in patients with moderate renal impairment.

Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on or previously treated with antiadrenergic agents. If a patient is undergoing cataract surgery, the ophthalmologist should be prepared for possible modifications of the surgical technique (iris hooks, iris dilator rings). There does not appear to be a benefit in stopping antiadrenergic agents therapy prior to the cataracts surgery.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.

The recommended dosage of pemigatinib should be reduced in patients with severe hepatic dysfunction. No dose adjustment is recommended for patients with mild or moderate hepatic impairment.

The recommended dosage of pemigatinib should be reduced in patients with severe renal disease. No dose adjustment is recommended for patients with mild or moderate renal impairment, or those patients with end-stage renal disease receiving intermittent hemodialysis.

Peripheral alpha 1- adrenergic receptor blocking agents (aka alpha 1- blockers) cause vasodilation and can produce marked hypotension, especially orthostatic hypotension with syncope or other postural symptoms such as dizziness, lightheadedness, and palpitations. Orthostatic effects are most common during initiation of therapy and often occur within 90 minutes after the first dose. However, they can also occur following a dosage increase or resumption of therapy after an interruption of more than a few days. Agents with alpha 1a specificity, such as tamsulosin, act primarily on the prostate but are not devoid of hypotensive effects. Therapy with peripheral alpha-1 blockers should be administered cautiously in patients with or predisposed to hypotensive or syncopal episodes. Caution is also advised in patients who are dehydrated (e.g., due to severe or prolonged diarrhea or vomiting), since they may be more sensitive to the hypotensive effect of the drugs. Therapy should be initiated with the lowest dosage possible and titrated gradually based on patient response and tolerance in accordance with the individual product package labeling. During initiation or reinstitution of therapy and following an increase in dosage, patients should be advised not to rise abruptly from a sitting or recumbent position and to avoid situations where injury could result if syncope occur. Concomitant use of alcohol, extensive periods of standing, prolonged or intense exercise, and exposure to heat can also precipitate orthostatic hypotension and should be minimized. If dizziness, lightheadedness or palpitations occur, the patient should sit or lie down, and seek medical attention if symptoms are recurrent or bothersome.

Pemigatinib can cause retinal pigment epithelial detachment (RPED), which may cause symptoms such as blurred vision, visual floaters, or photopsia. A comprehensive ophthalmological examination including an optical coherence tomography should be performed prior to treatment initiation. Patients with visual disturbances should be closely monitored.