"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing of selexipag (Uptravi, Actelion Registration Ltd) for the treatment of adults with pulmonary arterial hypertension (PAH)./"...
Patient Selection Considerations
Congestive Heart Failure Post-Myocardial Infarction
INSPRA is indicated to improve survival of stable patients with left ventricular (LV) systolic dysfunction (ejection fraction ≤ 40%) and clinical evidence of congestive heart failure (CHF) after an acute myocardial infarction (MI).
INSPRA is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. INSPRA may be used alone or in combination with other antihypertensive agents.
DOSAGE AND ADMINISTRATION
Congestive Heart Failure Post-Myocardial Infarction
Treatment should be initiated at 25 mg once daily and titrated to the recommended dose of 50 mg once daily, preferably within 4 weeks as tolerated by the patient. INSPRA may be administered with or without food.
Once treatment with INSPRA has begun, adjust the dose based on the serum potassium level as shown in Table 1.
Table 1: Dose Adjustment in Congestive Heart Failure
|Serum Potassium (mEq/L)||Action||Dose Adjustment|
|< 5.0||Increase||25 mg every other day to 25 mg once daily
25 mg once daily to 50 mg once daily
|5.5–5.9||Decrease||50 mg once daily to 25 mg once daily
25 mg once daily to 25 mg every other day
25 mg every other day to withhold
|≥ 6.0||Withhold||Restart at 25 mg every other day when potassium levels fall to < 5.5 mEq/L|
The recommended starting dose of INSPRA is 50 mg administered once daily. The full therapeutic effect of INSPRA is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily the dosage of INSPRA should be increased to 50 mg twice daily. Higher dosages of INSPRA are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia [see Clinical Studies].
Serum potassium should be measured before initiating INSPRA therapy, within the first week, and at one month after the start of treatment or dose adjustment. Serum potassium should be assessed periodically thereafter. Patient characteristics and serum potassium levels may indicate that additional monitoring is appropriate [see WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS]. In the EPHESUS study [see Clinical Studies], the majority of hyperkalemia was observed within the first three months after randomization.
In all patients taking INSPRA who start taking a moderate CYP3A4 inhibitor, check serum potassium and serum creatinine in 3-7 days.
Dose Modifications for Specific Populations
For hypertensive patients receiving moderate CYP3A4 inhibitors (e.g., erythromycin, saquinavir, verapamil, and fluconazole), the starting dose of INSPRA should be reduced to 25 mg once daily [see DRUG INTERACTIONS].
Dosage Forms And Strengths
- 25 mg tablets: yellow diamond biconvex film-coated tablets debossed with Pfizer on one side and NSR over 25 on the other
- 50 mg tablets: yellow diamond biconvex film-coated tablets debossed with Pfizer on one side and NSR over 50 on the other
Storage And Handling
INSPRA Tablets, 25 mg, are yellow diamond biconvex film-coated tablets. They are debossed with Pfizer on one side and NSR over 25 on the other. They are supplied as follows:
|0025-1710-01||Bottle of 30 tablets|
|0025-1710-02||Bottle of 90 tablets|
|0025-1710-03||Hospital Unit Dose|
INSPRA Tablets, 50 mg, are yellow diamond biconvex film-coated tablets. They are debossed with Pfizer on one side and NSR over 50 on the other. They are supplied as follows:
|0025-1720-03||Bottle of 30 tablets|
|0025-1720-01||Bottle of 90 tablets|
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [See USP Controlled Room Temperature].
Distributed by : G.D.Searle, Division of Pfizer Inc, NY, NY 10017. Revised: May 2013This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 6/3/2013
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