Niacin / Simvastatin

Pronunciation: NYE-a-sin/SIM-va-STAT-in
Class: Antihyperlipidemic combination

Trade Names

Simcor
- Tablets, oral niacin 500 mg ER/simvastatin 20 mg
- Tablets, oral niacin 500 mg ER/simvastatin 40 mg
- Tablets, oral niacin 750 mg ER/simvastatin 20 mg
- Tablets, oral niacin 1,000 mg ER/simvastatin 20 mg
- Tablets, oral niacin 1,000 mg ER/simvastatin 40 mg

Pharmacology

Niacin

Necessary for lipid metabolism, tissue respiration, and glycogenolysis; reduces total cholesterol, LDL cholesterol, and triglycerides while increasing HDL cholesterol.

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Simvastatin

Increases the rate at which the body removes cholesterol from blood and reduces production of cholesterol by inhibiting the enzyme that catalyzes an early rate-limiting step in cholesterol synthesis.

Indications and Usage

Reduce total cholesterol, LDL cholesterol, apolipoprotein B, non-HDL cholesterol, or triglycerides, or increase HDL cholesterol in patients with primary hypercholesterolemia and mixed dyslipidemia; reduce triglycerides in patients with hypertriglyceridemia.

Contraindications

Active liver disease or unexplained persistent elevations in hepatic transaminase levels; active peptic ulcer disease; arterial bleeding; women who are pregnant or may become pregnant; breast-feeding women; known hypersensitivity to any component of the product; coadministration with strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, boceprevir, telaprevir, posaconazole, telithromycin), cyclosporine, danazol, diltiazem, gemfibrozil, or verapamil.

Dosage and Administration

Adults

PO In patients not currently receiving niacin ER, start with niacin 500 mg ER/simvastatin 20 mg daily at bedtime. Patients already taking simvastatin 20 to 40 mg who need additional management of their lipid levels may be started on niacin 500 mg ER/simvastatin 40 mg at bedtime. The dosage of niacin ER should not be increased by more than 500 mg daily every 4 wk. The recommended maintenance dosage is niacin 1,000 mg ER/simvastatin 20 mg to niacin 2,000 mg ER/simvastatin 40 mg once daily (max dose, niacin 2,000 mg ER/simvastatin 40 mg daily).

Concomitant therapy

Do not exceed niacin 1,000 mg ER/simvastatin 20 mg per day in patients taking amiodarone, amlodipine, or ranolazine.

Renal Function Impairment

PO Do not start treatment in patients with severe renal impairment unless patient already tolerates treatment with simvastatin 10 mg or higher.

Chinese Patients

PO Use caution when treating Chinese patients with dosages that exceed niacin 1,000 mg ER/simvastatin 20 mg per day.

General Advice

  • Administer once daily at bedtime with a low-fat snack.
  • If therapy is discontinued for more than 7 days, retitration as tolerated is recommended.
  • Tablets should be taken whole; do not to break, crush, or chew before swallowing.
  • Avoid administration on an empty stomach.
  • Concomitant alcoholic drinks, hot drinks, or spicy foods should be avoided.
  • Flushing may be reduced in frequency or severity by pretreatment with aspirin at a dose up to 325 mg (approximately 30 minutes prior to dose).
  • Simcor should only be substituted for equivalent doses of niacin ER ( Niaspan ). Do not substitute with other modified-release (eg, sustained-release, timed-release) niacin or immediate-release niacin.

Storage/Stability

Store between 68° and 77°F.

Drug Interactions

No drug interaction studies have been conducted with niacin/simvastatin. The following interactions have been noted with the individual components of niacin/simvastatin.

Alcohol/Hot drinks

Concomitant alcohol or hot drinks may increase the adverse reactions of flushing and pruritus with niacin. Advise patients to avoid alcohol or hot drinks around the time of ingestion of niacin ER/simvastatin tablets.

Amiodarone, ranolazine

Coadministration may result in myopathy or rhabdomyolysis. Do not exceed niacin 1,000 mg ER/simvastatin 20 mg daily during coadministration.

Antihypertensive therapy (eg, ganglionic-blocking agents, vasoactive agents)

Niacin may potentiate the effects of these agents, resulting in postural hypotension. Coadminister with caution.

Aspirin

Metabolic Cl of niacin may be decreased. The clinical relevance of this finding is unclear.

Azole antifungal agents (eg, itraconazole, ketoconazole, posaconazole), cyclosporine, danazol, gemfibrozil, hepatic C virus protease inhibitors (eg, boceprevir, telaprevir), macrolide antibiotics (eg, clarithromycin, erythromycin, telithromycin), mifepristone, nefazodone, protease inhibitors (eg, nelfinavir, ritonavir)

May increase the risk of myopathy and rhabdomyolysis. Coadministration is contraindicated.

Bile acid sequestrants (eg, cholestyramine, colestipol)

Because niacin may bind to these agents, separate the administration times by as much as possible (at least 4 to 6 h).

Bosentan, carbamazepine, efavirenz, hydantoins (eg, phenytoin), rifamycins (eg, rifampin)

Simvastatin metabolism may be increased, resulting in a decrease in simvastatin plasma levels and efficacy. If coadministration cannot be avoided, closely monitor the clinical response of the patient.

Calcium channel blockers (eg, amlodipine, diltiazem, verapamil)

Coadministration may result in elevated plasma levels of simvastatin, increasing the risk of toxicity (eg, rhabdomyolysis, myositis). With coadministration of amlodipine and simvastatin, the dosage of simvastatin should not exceed 20 mg/day. Because doses of simvastatin are not to exceed 10 mg when administered with diltiazem or verapamil and all doses of niacin/simvastatin contain more than 10 mg, diltiazem and verapamil are contraindicated with niacin/simvastatin.

Colchicine

Myopathy and rhabdomyolysis have been reported. Coadminister with caution.

Conivaptan

Simvastatin plasma concentrations may be elevated, increasing the risk of myopathy. Suspend concomitant use and restart niacin/simvastatin at least 1 week after conivaptan therapy is completed.

Daptomycin

The risk of myopathy/rhabdomyolysis is increased. Consider a temporary suspension of niacin/simvastatin in patients receiving daptomycin.

Delavirdine, dronedarone, fluconazole, imatinib, quinupristin/dalfopristin, sirolimus, tacrolimus, voriconazole

Simvastatin plasma concentrations may be elevated, increasing the risk of myopathy. If coadministration cannot be avoided, advise patients to report any unexplained muscle pain, tenderness, or weakness. The simvastatin dose should not exceed 10 mg/day in patients taking dronedarone. Because all doses of niacin/simvastatin contain more than 10 mg of simvastatin, do not coadminister.

Digoxin

Digoxin plasma concentrations may be elevated. Clinical and laboratory monitoring is warranted. Adjust the digoxin dose as needed.

Fenofibrate

May increase the risk of myopathy and rhabdomyolysis. Avoid coadministration.

Pazopanib

Coadministration may increase the risk of pazopanib-related liver injury.

Propranolol

Simvastatin plasma levels may be decreased. The clinical relevance of this finding is unclear.

St. John's wort

May decrease simvastatin levels; avoid coadministration.

Warfarin

Increased INR has been demonstrated with coadministration. Carefully monitor anticoagulant parameters and adjust the warfarin dose as needed.

Food Grapefruit juice

Coadministration of grapefruit juice (more than 1 quart daily) may increase simvastatin serum concentrations and adverse reactions (eg, rhabdomyolysis). Avoid coadministration. Coadministration of more than 1 quart daily of grapefruit juice is contraindicated.

Oat bran/pectin

The pharmacologic effects of simvastatin may be decreased because of decreased GI absorption when taken with pectin or oat bran. Oat bran or pectin and simvastatin should not be taken at the same time; separate simvastatin administration by as much time as possible.

Peppermint oil

Simvastatin levels may be elevated, increasing the pharmacologic and adverse reactions. Coadminister with caution.

Adverse Reactions

The following adverse reactions were reported with Simcor administration. Adverse reactions occurring with administration of either niacin or simvastatin are listed in their respective monographs.

CNS

Headache (5%).

Dermatologic

Flushing (59%); pruritus (3%).

GI

Diarrhea, nausea (3%).

Lab Tests

Abnormal thyroid function tests; elevated alkaline phosphatase, amylase, bilirubin, creatine kinase, fasting blood glucose, GGT, LDH, serum transaminases, and uric acid; decreased phosphorus and platelet counts; prolonged PT.

Musculoskeletal

Back pain (3%).

Precautions

Monitor

Closely monitor patients with renal impairment. Carefully monitor for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial month of treatment or during any period of upward dosage titration of either drug. Monitor lipid panel at regular intervals. Obtain LFTs prior to initiating therapy and repeat as clinically indicated. Closely observe diabetic or potentially diabetic patients during treatment with niacin/simvastatin, particularly during the first few months of therapy.


Pregnancy

Category X . May cause fetal harm.

Lactation

Niacin

Excreted in breast milk.

Simvastatin

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Hypersensitivity

Has been reported.

Renal Function

Use with caution.

Hepatic Function

Contraindicated in active liver disease or unexplained transaminase elevations. Use with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease.

Laboratory Test Abnormalities

Increased fasting glucose, platelet count, PT, and uric acid may occur.

Endocrine effect

Increases in HbA 1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.

Hepatic effects

Severe hepatic toxicity, including fulminant hepatic necrosis, has occurred in patients substituting sustained-release niacin for immediate-release niacin in equivalent doses. Niacin ER and simvastatin can cause abnormal LFTs.

Myopathy/Rhabdomyolysis

Has been reported with simvastatin. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred.

Surgery

Stop therapy for a few days before elective major surgery and when any major medical or surgical condition supervenes.

Overdosage

Symptoms

Insufficient data. Patients have recovered from a simvastatin overdose of 3.6 g without sequelae.

Patient Information

  • Advise patients to take this medication at bedtime, after a low-fat snack.
  • Advise patients that this medication should be swallowed whole and not to break, crush, or chew tablets.
  • Advise patients that if dosing is interrupted for any length of time, they should contact their health care provider before restarting therapy.
  • Instruct patients to immediately notify their health care provider if they experience any unexplained muscle pain, tenderness, or weakness.
  • Advise patients that if bothersome flushing occurs, taking aspirin 30 min before taking niacin ER/simvastatin may minimize flushing.
  • Caution patients that if flushing awakens them during the night, to rise slowly to reduce the chances of dizziness or fainting.
  • Advise patients to avoid ingestion of alcohol, hot beverages, and spicy foods around the time they take niacin ER/simvastatin to minimize flushing.
  • Instruct diabetic patients to monitor their blood glucose more frequently when this medication is started or the dose is changed, and to notify their health care provider of changes in blood glucose readings.
  • Advise women of childbearing age to use an effective method of birth control.
  • Advise women who are breast-feeding not to use this medicine.
  • Advise patients to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.

Copyright © 2009 Wolters Kluwer Health.

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