Niacin / Lovastatin

Pronunciation: NYE-uh-sin/LOW-vuh-STAT-in
Class: Antihyperlipidemic combination

Trade Names

Advicor
- Tablets 500/20 mg
- Tablets 750/20 mg
- Tablets 1,000/20 mg
- Tablets 1,000/40 mg

Pharmacology

Niacin

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

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Lovastatin

Increases rate at which body removes cholesterol from blood and reduces production of cholesterol in body by inhibiting enzyme that catalyses early rate-limiting step in cholesterol synthesis; increases HDL; reduces LDL, VLDL, and TG.

Pharmacokinetics

Absorption

C max of niacin averaged about 18 mcg/mL about 5 h after dosing; lovastatin C max averaged about 11 ng/mL about 2 h after dosing. The extent of niacin and lovastatin absorption was increased by administration with food.

Distribution

Niacin is less than 20% bound to human serum proteins and distributes into milk. Niacin and its metabolites concentrate in the liver, kidney, and adipose tissue. Both lovastatin and its beta-hydroxyacid metabolite are highly bound (more than 95%) to human plasma proteins. Lovastatin is concentrated in the liver and crosses the blood-brain and placental barriers.

Metabolism

Niacin undergoes rapid and extensive first-pass metabolism forming nicotinuric acid and nicotinamide. Lovastatin undergoes extensive first-pass extraction and metabolism by CYP-450 3A4 in the liver. The major active metabolites are the beta-hydroxyacid of lovastatin (lovastatin acid), its 6'-hydroxy derivative.

Elimination

Niacin is primarily excreted in urine mainly as metabolites. The plasma t ½ was about 4.5 hours for lovastatin and about 20 to 48 minutes for niacin.

Indications and Usage

Treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Frederickson Types IIa and IIb) in patients treated with lovastatin who require further TG-lowering or HDL-raising who may benefit from having niacin added to their regimen; patients treated with niacin who require further LDL-lowering who may benefit from having lovastatin added to their regimen.

Contraindications

Pregnancy, lactation, active liver disease, unexplained persistent elevations in serum transaminases, active peptic ulcer disease, arterial bleeding, hypersensitivity to any component of product.

Dosage and Administration

Adults

PO Patients receiving a stable dose of Niaspan (niacin extended-release tablets) may be switched directly to a niacin-equivalent dose of Advicor . Patients receiving a stable dose of lovastatin may receive concomitant dosage titration with Niaspan and switch to Advicor once a stable dose of Niaspan has been reached. Advicor should be taken at bedtime.

General Advice

  • Administer prescribed dose at bedtime with a low-fat snack.
  • Do not increase dose by more than 500 mg daily (based on extended-release niacin component) every 4 wk.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F).

Drug Interactions

Antihypertensive therapy (eg, ganglionic agents, vasoactive agents)

Niacin may potentiate effects resulting in postural hypotension.

Aspirin

Metabolic Cl of niacin may be decreased.

Bile acid sequestrants

Because of possible binding of niacin to these agents, allow 4 to 6 h (or as long an interval as possible) to elapse between the ingestion of bile acid-binding resins and administration of Advicor .

Clarithromycin, cyclosporine, erythromycin, gemfibrozil, HIV protease inhibitors (eg, ritonavir), itraconazole, ketoconazole, nefazodone, niacin

May increase the risk of skeletal muscle disorders (eg, rhabdomyolysis).

Coumarin anticoagulants (eg, warfarin)

Bleeding and increased PT may occur. Monitor anticoagulant parameters when starting, stopping, or changing the Advicor dose.

Hot beverages or alcohol

May increase the adverse reactions of flushing and pruritus with niacin and should be avoided.

Laboratory Test Interactions

Niacin may produce false elevations in some fluorometric determinations of plasma or urinary catecholamines; niacin may give false-positive reactions with cupric sulfate solution ( Benedicts reagent) in urine glucose tests.

Adverse Reactions

The incidence stated for the following adverse reactions were reported with Advicor (niacin/lovastatin) administration. Adverse reactions occurring with administration of either niacin or lovastatin listed in their respective monographs.

CNS

Headache (9%); asthenia (5%).

Dermatologic

Flushing (71%); pruritus (7%); rash (5%).

GI

Nausea (7%); diarrhea (6%); abdominal pain (4%); dyspepsia, vomiting (3%).

Metabolic-Nutritional

Hyperglycemia (4%).

Musculoskeletal

Back pain (5%); myalgia (3%).

Miscellaneous

Infection (20%); pain (8%); flu syndrome (6%).

Precautions

Monitor

Monitor blood sugar in diabetic patient when drug is started or dose is changed. Assess fasting blood glucose before starting therapy and periodically thereafter during therapy in patient with risk factors for diabetes mellitus (eg, obesity, family history of diabetes). Assess serum transaminases before starting therapy, every 6 to 12 wk for the first 6 mo of therapy, and periodically (eg, every 6 mo) thereafter as clinically indicated.


Pregnancy

Category X .

Lactation

Niacin

Excreted in breast milk.

Lovastatin

Undetermined.

Children

Safety and efficacy not established.

Special Risk Patients

Use with caution in patients with unstable angina or in the acute phase of MI, or in patients predisposed to gout; use with caution in patients with a history of jaundice or hepatobiliary disease; administer with caution in patients with peptic ulcers and in patients who consume substantial quantities of alcohol and/or who have a history of liver disease.

Dose equivalence

Equivalent doses of Advicor may be substituted for equivalent doses of Niaspan but should not be substituted for other modified-release niacin preparations or immediate-release niacin preparations.

Fasting blood sugar

A dose related rise may be experienced in diabetic patients.

Liver dysfunction

Severe hepatic toxicity, including fulminant hepatic necrosis, has occurred in patients substituting sustained-release niacin for immediate-release niacin in equivalent doses.

Myopathy/Rhabdomyolysis

Have been reported when lovastatin is used in combination with lipid altering doses (at least 1 g/day) of niacin.

Transaminase levels

Because lovastatin may increase creatine phosphokinase and transaminase levels, this should be considered in differential diagnosis of chest pain.

Overdosage

Symptoms

Niacin

Severe flushing, nausea, vomiting, diarrhea, dyspepsia, dizziness, syncope, hypotension, possible cardiac arrhythmias, clinical laboratory abnormalities.

Patient Information

  • Explain LDL-C and TG goals.
  • Advise patient that dose of medication may change, based on results of cholesterol and TG blood tests, in an effort to reach LDL-C and TG goals.
  • Review other substances (eg, grapefruit juice) and medications (eg, potent CYP3A4 inhibitors, nutritional supplements containing niacin or nicotinamide) that should not be taken with this medication.
  • Advise patient to take prescribed dose once daily at bedtime with a low-fat snack.
  • Instruct patient to swallow tablets whole and not to crush, chew, or break the tablets.
  • Caution patient that taking this medication on an empty stomach increases the risk of experiencing flushing, itching, and stomach distress.
  • Caution patient that drinking alcohol or hot drinks around the time of medication administration will increase the risk of flushing.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Caution patient that if medication is not taken for an extended length of time (eg, more than 7 days) to contact health care provider before restarting the medication. Advise patient that retitration of the dose of medication may be required.
  • Emphasize to patient importance of other modalities on cholesterol control: dietary changes (reduced saturated fat intake, increase soluble fiber intake), weight control, regular exercise, smoking cessation.
  • Advise patient that drug helps control, but not does cure, cholesterol abnormality and to continue taking drug as prescribed when LDL-C and TG goals have been met.
  • Instruct patient to continue taking other cholesterol-lowering medications as prescribed by health care provider.
  • Advise patient that flushing, which may last for several hours after dosing, is a common adverse reaction of therapy but that it usually goes away after several weeks of consistent use.
  • Caution patient that if flushing awakens them during the night to rise slowly to reduce the chances of dizziness or fainting.
  • Advise patient that if flushing occurs and is bothersome, that taking aspirin or another NSAID (eg, ibuprofen) 30 minute before taking niacin/lovastatin may minimize flushing.
  • Advise patient who also is taking a bile acid sequestrant (eg, cholestyramine) to take the niacin/lovastatin at least 2 h before or 4 h or more after the sequestrant.
  • Instruct patient to immediately notify health care provider if experiencing any unexplained muscle pain, tenderness and/or weakness, unquenchable thirst, frequent urination, frequent episodes of dizziness, fainting, or if any other unusual or unexplained feelings are noted.
  • Instruct diabetic patient to monitor blood glucose more frequently when drug is started or dose is changed and to inform health care provider of significant changes in readings.
  • Advise women of childbearing potential to use effective contraception during treatment with niacin/lovastatin.
  • Caution patient not to take any other forms of niacin, or nicotinamide unless advised by health care provider.

Copyright © 2009 Wolters Kluwer Health.

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