RJ is a 52 yo M who comes into your pharmacy with a new prescription for Ranexa 500 mg PO QD for his newly diagnosed stable angina. RJ’s past medical history includes hypertension, hyperlipidemia, depression, gastroparesis and benign prostatic hyperplasia. 

Current medications:

Lisinopril 40 mg QD

Simvastatin 40 mg QHS

Citalopram 20 mg QD

Tadalafil 5 mg QD

Zofran 4mg PO q8h for nausea

Prior to dispensing the new prescription for Ranexa, you have some concerns and decide to call the prescriber. Which of the following would be appropriate to discuss with them? Select all that apply.

A. Ranexa is contraindicated with tadalafil therapy

B. Changing Ranexa to 500 mg BID 

C. Decreasing simvastatin to 20 mg daily

D. Concomitant use with lisinopril increases the risk of hyperkalemia

E. There is a potential increased risk of QT prolongation with RJ's other medications

Answer with rationale

Stable angina occurs when myocardial oxygen demand exceeds oxygen supply causing chest discomfort. Ranexa is an antianginal agent that exerts its effects via the inhibition of sodium channels during repolarization. It decreases intracellular sodium concentrations thus decreasing calcium influx into the cell. The decreased intracellular calcium levels reduces myocardial oxygen demand through ventricular muscle relaxation and decreased oxygen consumption. 

Ranexa is extensively metabolized in the liver and is contraindicated in liver cirrhosis. It should be avoided with strong CYP3A4 inhibitors and inducers. When a patient is taking Ranexa, it is important to monitor ECG and renal function, as it can cause QT prolongation and ranolazine therapy should in most circumstances not be initiated when a patient’s CrCl is less than 30 mL/min as this has been associated with acute kidney injury. The most common side effects seen with Ranexa include dizziness, headache, constipation, and nausea. 

Answer A is incorrect. There is no drug-drug interaction between Ranexa and tadalafil. Nitroglycerin is a drug commonly used to relieve anginal symptoms, and its use should be avoided within 48 hours of tadalafil to avoid a potentially dangerous decrease in blood pressure. 

Answer B is correct. The starting dose of Ranexa for chronic stable angina is 500 mg BID, and it can be titrated up to 1,000 mg BID if needed based on symptoms.

Answer C is correct. When Ranexa and simvastatin are taken together, simvastatin cannot exceed 20 mg/day. Ranexa is known to increase concentrations of simvastatin, and doses higher than 20 mg/day increase the risk for rhabdomyolysis and myalgias.  

Answer D is incorrect. Lisinopril has the potential to cause hyperkalemia through its inhibition of the angiotensin converting enzyme. Ranexa neither directly increases nor decreases potassium levels. 

Answer E is correct. Citalopram, Ranexa, and Zofran all have the potential to prolong the QT interval. There are additive risks of QT prolongation with each subsequent medication a patient is taking. Some of the most important risks of progressing to drug-induced Torsades des pointes include previous history of QT prolongation or concomitant hypokalemia and/or hypomagnesemia. 

Brand/Generic: citalopram (Celexa), lisinopril (Prinivil, Zestril), ranolazine (Ranexa), simvastatin (Zocor), tadalafil (Cialis)

NAPLEX Content Domains Covered:

1.A.1 Pharmacology

1.A.2 Pharmacokinetics

2.A.2 Dosing regimens

3.C.2 Appropriateness of therapy

3.C.3 Drug-drug interactions