Interactions between Dabrafenib and Finasteride / tadalafil

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Alcoholism.

Alcohol consumption may intensify the pressure-lowering effects of mild vasodilators, such as phosphodiesterase 5 (PDE5) inhibitors. Therefore, patients that consume alcohol should be warned to limit alcohol intake while receiving these agents.

Dabrafenib has a moderate potential interaction with Bleeding Disorder.

The use of dabrafenib may increase the chance of hemorrhagic events. Care should be exercised when using this drug in patients who have had bleeding problems or who plan to have surgery, dental, or other medical procedures. Dabrafenib should be permanently discontinued for all grade 4 hemorrhagic events and for any grade 3 hemorrhagic events that do not improve. Dabrafenib should be withheld for grade 3 hemorrhagic events; if improved, this drug should resume at the next lower dose level.

The tadalafil in finasteride / tadalafil has a major potential interaction with Cardiovascular Conditions and Disorders.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

The tadalafil in finasteride / tadalafil has a major potential interaction with Cerebral Vascular Disorder.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

Dabrafenib has a moderate potential interaction with Dermatitis, Drug-Induced.

The use of dabrafenib may result in severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal. Care should be exercised when using this drug in patients at risk of skin toxicities. Patients should be monitored for new or worsening serious skin reactions. Dabrafenib should be permanently discontinued for SCARs. For other skin toxicities, dabrafenib should be withheld for intolerable or severe skin toxicity and should resume at a lower dose upon improvement or recovery within 3 weeks. Dabrafenib should be permanently discontinued if skin toxicity has not improved within 3 weeks.

Dabrafenib has a moderate potential interaction with Diabetes Mellitus.

In clinical trials, patients with a history of diabetes who received dabrafenib required more intensive hypoglycemic therapy. Care should be exercised when using this drug in patients with preexisting diabetes or hyperglycemia. Serum glucose levels should be monitored at the start of therapy and as clinically indicated in these patients. Antihyperglycemic medications should be started or optimized as clinically indicated.

Dabrafenib has a moderate potential interaction with Fever.

Serious febrile reactions and fever of any severity complicated by rigors/chills, hypotension, dehydration, and/or renal failure have been observed with the use of dabrafenib. The incidence and severity of pyrexia are increased when this drug is administered in combination with trametinib compared with dabrafenib as a single agent. It is recommended to withhold therapy for temperature of 38C (100.4F) or higher; in case of recurrence, therapy can be interrupted at first symptom of pyrexia. Patients should be evaluated for signs/symptoms of infection, and it is recommended to monitor serum creatinine and other evidence of renal function during and after severe pyrexia. Antipyretics should be administered as secondary prophylaxis when resuming therapy for patients with prior episode of severe febrile reaction or fever associated with complications. Corticosteroids (e.g., prednisone 10 mg/day) should be administered for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of pyrexia onset, or for pyrexia associated with complications, and there is no evidence of active infection. Upon resolution of pyrexia, dose reduction and/or permanent therapy discontinuation may be required.

Dabrafenib has a moderate potential interaction with G-6-PD Deficiency.

Dabrafenib contains a sulfonamide moiety. Care should be exercised when using this drug in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency as it may increase the risk of hemolytic anemia. Patients with G6PD deficiency should be monitored for signs of hemolytic anemia while taking dabrafenib.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Hearing Loss.

Use of phosphodiesterase-5 (PDE5) inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. Patients with hearing problems should stop taking these agents and seek prompt medical care.

Dabrafenib has a moderate potential interaction with Heart Disease.

Cardiomyopathy (defined as a reduction in left ventricular ejection fraction [LVEF] at least 10% from baseline and below the institutional lower limit of normal [LLN]) has been reported with the use of dabrafenib in combination with trametinib. Caution should be exercised when using this drug in patients with heart problems. It is recommended to assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before starting therapy, 1 month after starting, and then every 2 to 3 months while on treatment. Dabrafenib should be withheld for symptomatic cardiomyopathy or asymptomatic left ventricular dysfunction of greater than 20% from baseline that is below institutional LLN. Dabrafenib should resume at the same dose level upon recovery of cardiac function to at least the institutional LLN for LVEF and absolute decrease up to 10% compared to baseline.

The tadalafil in finasteride / tadalafil has a major potential interaction with History - Cerebrovascular Disease.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

The tadalafil in finasteride / tadalafil has a major potential interaction with History - Myocardial Infarction.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

The tadalafil in finasteride / tadalafil has a major potential interaction with Hypotension.

The use of phosphodiesterase-5 (PDE5) inhibitors is not recommended in patients with preexisting cardiovascular disease for whom sexual activity is inadvisable due to the potential cardiac risk. Physicians should also consider the vasodilatory effect of these drugs and whether they may adversely affect patients with underlying cardio- and/or cerebrovascular conditions, in particular those who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months; those with resting hypotension (BP < 90/50) or hypertension (BP > 170/110); and those with unstable angina associated with cardiac failure or coronary artery disease. There are no controlled clinical data on the safety or efficacy in such patients. Other adverse cardiovascular effects reported include angina pectoris, myocardial infarction, AV block, ventricular arrhythmia, tachycardia, palpitation, hypotension, postural hypotension, syncope, cerebral thrombosis, cerebrovascular hemorrhage, transient ischemic attack, cardiac arrest, heart failure, and hypertension. Many of these events occurred in patients with cardiovascular risk factors and during or shortly after sexual activity.

Dabrafenib has a moderate potential interaction with Infection.

Serious febrile reactions and fever of any severity complicated by rigors/chills, hypotension, dehydration, and/or renal failure have been observed with the use of dabrafenib. The incidence and severity of pyrexia are increased when this drug is administered in combination with trametinib compared with dabrafenib as a single agent. It is recommended to withhold therapy for temperature of 38C (100.4F) or higher; in case of recurrence, therapy can be interrupted at first symptom of pyrexia. Patients should be evaluated for signs/symptoms of infection, and it is recommended to monitor serum creatinine and other evidence of renal function during and after severe pyrexia. Antipyretics should be administered as secondary prophylaxis when resuming therapy for patients with prior episode of severe febrile reaction or fever associated with complications. Corticosteroids (e.g., prednisone 10 mg/day) should be administered for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of pyrexia onset, or for pyrexia associated with complications, and there is no evidence of active infection. Upon resolution of pyrexia, dose reduction and/or permanent therapy discontinuation may be required.

Dabrafenib has a moderate potential interaction with Liver Disease.

Hepatic metabolism and biliary secretion are the primary routes of elimination of dabrafenib and its metabolites; thus, patients with moderate (bilirubin greater than 1.5 to 3 times the upper limit of normal [1.5 to 3 x ULN] and any AST) or severe (bilirubin greater than 3 to 10 x ULN and any AST) liver dysfunction may have increased exposure. An appropriate dosage has not been established for patients with moderate or severe liver dysfunction; care should be exercised when using dabrafenib in these patients. Dose adjustment is not recommended for patients with mild liver dysfunction (bilirubin up to ULN and AST greater than ULN or bilirubin greater than 1 to 1.5 x ULN and any AST).

The finasteride in finasteride / tadalafil has a moderate potential interaction with Liver Disease.

Finasteride and dutasteride are extensively metabolized by the liver. Therapy with these drugs should be administered cautiously in patients with liver disease as exposure could be higher.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Liver Disease.

Phosphodiesterase 5 (PDE-5) inhibitors are cleared predominantly by hepatic metabolism. The pharmacokinetic disposition of these agents has not been assessed in patients with severe hepatic impairment. No dosage modification is recommended for patients with mild to moderate hepatic impairment, however, therapy with these agents should not be administered to patients with severe hepatic impairment. In patients with mild hepatic impairment a lower dose of these agents should be used as initial therapy.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Myeloproliferative Disorders.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Optic Nerve Disorder.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Penis Disorders.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Peyronie Disease.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

The tadalafil in finasteride / tadalafil has a major potential interaction with Pulmonary Edema.

Tadalafil tablet for the treatment of pulmonary arterial hypertension (PAH) should not be used in patients with pulmonary veno-occlusive disease (PVOD) as it may significantly worsen the cardiovascular status of these patients. If signs of pulmonary edema develop during therapy, the possibility of associated PVOD should be considered.

The tadalafil in finasteride / tadalafil has a major potential interaction with Pulmonary Heart or Vascular Disease.

Tadalafil tablet for the treatment of pulmonary arterial hypertension (PAH) should not be used in patients with pulmonary veno-occlusive disease (PVOD) as it may significantly worsen the cardiovascular status of these patients. If signs of pulmonary edema develop during therapy, the possibility of associated PVOD should be considered.

The tadalafil in finasteride / tadalafil has a major potential interaction with Renal Dysfunction.

The plasma clearance of phosphodiesterase-5 (PDE5) inhibitors may be decreased in patients with severe renal impairment, resulting in drug accumulation. Therapy with these agents should be avoided in patients with severe renal disease or on renal dialysis. Dose adjustments might be needed based on individual renal assessment and tolerability if used in these patients.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Retinitis Pigmentosa.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Retinitis Pigmentosa.

Phosphodiesterase-5 (PDE5) inhibitors have been associated with transient impairment of color discrimination (blue/green) and blue- or color-tinged vision. These agents also inhibit phosphodiesterase-6 (PDE6), to a much lesser extent, which is involved in phototransduction in the retina. There are no controlled clinical data on the safety in patients with retinitis pigmentosa, a minority of whom may have genetic disorders of retinal phosphodiesterases. Therapy with these agents should be avoided in such patients.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Seizures.

The use of phosphodiesterase 5 (PDE-5) inhibitors has been associated with seizures. Therapy with these agents should be administered cautiously in patients with preexisting seizure disorders.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Sickle Cell Anemia.

Prolonged erection greater than 4 hours and priapism (painful erections greater than 6 hours) have been reported during treatment with phosphodiesterase-5 (PDE 5) inhibitors. Priapism may result in penile tissue damage and permanent loss of potency if not treated promptly. These agents should be used cautiously in patients with conditions that may predispose them to priapism such as sickle cell anemia, multiple myeloma, or leukemia, and those with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). If an erection persists longer than 4 hours, the patient should seek immediate medical assistance.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Tinnitus.

Use of phosphodiesterase-5 (PDE5) inhibitors has been associated with sudden decrease or loss of hearing, which may be accompanied by tinnitus or dizziness. Patients with hearing problems should stop taking these agents and seek prompt medical care.

The finasteride in finasteride / tadalafil has a moderate potential interaction with Urinary Tract Obstruction.

Patients with large residual urinary volume and/or severely diminished urinary flow should be carefully monitored for obstructive uropathy. These patients may not be candidates for finasteride therapy.

The tadalafil in finasteride / tadalafil has a moderate potential interaction with Visual Defect/Disturbance.

Tadalafil for the treatment of erectile dysfunction (ED) should be used with caution and only if the benefit outweighs the risk in patients with a history of non-arteritic anterior ischemic optic neuropathy (NAION) or with retinitis pigmentosa. Use of tadalafil for the treatment of pulmonary arterial hypertension is not recommended in patients with retinitis pigmentosa. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil; patients taking tadalafil for ED should immediately stop treatment. Most patients who developed NAION during therapy with tadalafil had underlying anatomic or vascular risk factors, including low cup to disc ratio ("crowded disc").