Advicor

Name: Advicor

Uses of Advicor

Advicor is a prescription medication used to treat high cholesterol, known medically as hypercholesterolemia.  

This medication may be prescribed for other uses.  Ask your doctor or pharmacist for more information.

Side Effects of Advicor

Serious side effects have been reported with Advicor.  See the "Advicor Precautions" section.

Common side effects of Advicor include the following:

  • flushing
  • headache
  • infection
  • rash/itching
  • nausea
  • diarrhea
  • high blood sugar (hyperglycemia)
  • stomach pain

This is not a complete list of Advicor side effects.  Ask your doctor or pharmacist for more information.  Tell your doctor if you have any side effect that bothers you or that does not go away.  Call your doctor for medical advice about side effects.  You may report side effects to the FDA at 1-800-FDA-1088.

Inform MD

Before taking Advicor, tell your doctor about all of your medical conditions.  Especially tell your doctor if you:

  • are allergic to Advicor or to any of its ingredients
  • have liver problems
  • have heart problems
  • have diabetes
  • have a past history of jaundice, hepatobiliary disease, or peptic ulcer
  • are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Advicor Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Cough or hoarseness
  • feeling of warmth
  • fever or chills
  • lower back or side pain
  • pain
  • painful or difficult urination
  • redness, itching, or tingling of the face, neck, arms, and occasionally, upper chest
Less common
  • Abdominal or stomach pain
  • blurred vision
  • cramping pain or stiffness
  • difficulty moving
  • dry mouth
  • dry skin
  • fruit-like breath odor
  • increased hunger
  • increased thirst
  • increased urination
  • joint pain
  • muscle aches, weakness, tenderness, or pain
  • nausea
  • swollen joints
  • unexplained weight loss
  • unusual tiredness or weakness
  • vomiting
Rare
  • Dark-colored urine
  • muscle cramps, pain, spasm, or stiffness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
  • general feeling of discomfort or illness
  • headache
  • itching skin
  • loss of appetite
  • nausea
  • rash
  • runny nose
  • shivering
  • shortness of breath
  • sore throat
  • sweating
  • trouble sleeping
Less common
  • Acid or sour stomach
  • belching
  • heartburn
  • indigestion
  • lack or loss of strength
  • stomach discomfort or upset

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How is this medicine (Advicor) best taken?

Use Advicor (niacin and lovastatin) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • To gain the most benefit, do not miss doses.
  • Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
  • Take at bedtime after a low-fat snack.
  • Do not take on an empty stomach.
  • Swallow whole. Do not chew, break, or crush.
  • Avoid alcohol, hot drinks, or spicy foods when it is time to take Advicor.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you stop taking this medicine, talk with your doctor. You may need to be restarted at a lower dose and raise the dose slowly.

Precautions

General

Before instituting therapy with a lipid-altering medication, an attempt should be made to control dyslipidemia with appropriate diet, exercise, and weight reduction in obese patients, and to treat other underlying medical problems (see INDICATIONS AND USAGE).

Patients with a past history of jaundice, hepatobiliary disease, or peptic ulcer should be observed closely during Advicor therapy. Frequent monitoring of liver function tests and blood glucose should be performed to ascertain that the drug is producing no adverse effects on these organ systems.

Diabetic patients may experience a dose-related rise in fasting blood sugar (FBS). In three clinical studies, which included 1028 patients exposed to Advicor (6 to 22% of whom had diabetes type II at baseline), increases in FBS above normal occurred in 46 to 65% of patients at any time during study treatment with Advicor. Fourteen patients (1.4%) were discontinued from study treatment: 3 patients for worsening diabetes, 10 patients for hyperglycemia and 1 patient for a new diagnosis of diabetes. In the studies in which lovastatin and NIASPAN were used as active controls, 24 to 41% of patients receiving lovastatin and 43 to 58% of patients receiving NIASPAN also had increases in FBS above normal. One patient (1.1%) receiving lovastatin was discontinued for hyperglycemia. Diabetic or potentially diabetic patients should be observed closely during treatment with Advicor, and adjustment of diet and/or hypoglycemic therapy may be necessary.

In one long-term study of 106 patients treated with Advicor, elevations in prothrombin time (PT) >3 times ULN occurred in 2 patients (2%) during study drug treatment. In a long-term study of 814 patients treated with Advicor, 7 patients were noted to have platelet counts <100,000 during study drug treatment. Four of these patients were discontinued, and one patient with a platelet count <100,000 had prolonged bleeding after a tooth extraction. Prior studies have shown that NIASPAN can be associated with dose-related reductions in platelet count (mean of -11% with 2000 mg) and increases of PT (mean of approximately +4%). Accordingly, patients undergoing surgery should be carefully evaluated. In controlled studies, Advicor has been associated with small but statistically significant dose-related reductions in phosphorus levels (mean of -10% with 2000 mg/40 mg). Phosphorus levels should be monitored periodically in patients at risk for hypophosphatemia. In clinical studies with Advicor, hypophosphatemia was more common in males than in females. The clinical relevance of hypophosphatemia in this population is not known.

Niacin

Caution should also be used when Advicor is used in patients with unstable angina or in the acute phase of MI, particularly when such patients are also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents.

Elevated uric acid levels have occurred with niacin therapy; therefore, in patients predisposed to gout, niacin therapy should be used with caution. Niacin is rapidly metabolized by the liver, and excreted through the kidneys. Advicor is contraindicated in patients with significant or unexplained hepatic dysfunction (see CONTRAINDICATIONS and WARNINGS) and should be used with caution in patients with renal dysfunction.

Lovastatin

Lovastatin may elevate creatine phosphokinase and transaminase levels (see WARNINGS and ADVERSE REACTIONS). This should be considered in the differential diagnosis of chest pain in a patient on therapy with lovastatin.

Endocrine function - Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including lovastatin.

HMG-CoA reductase inhibitors interfere with cholesterol synthesis and as such might theoretically blunt adrenal and/or gonadal steroid production. Results of clinical studies with drugs in this class have been inconsistent with regard to drug effects on basal and reserve steroid levels. However, clinical studies have shown that lovastatin does not reduce basal plasma cortisol concentration or impair adrenal reserve, and does not reduce basal plasma testosterone concentration. Another HMG-CoA reductase inhibitor has been shown to reduce the plasma testosterone response to human chorionic gonadotropin (HCG). In the same study, the mean testosterone response to HCG was slightly but not significantly reduced after treatment with lovastatin 40 mg daily for 16 weeks in 21 men. The effects of HMG-CoA reductase inhibitors on male fertility have not been studied in adequate numbers of male patients. The effects, if any, on the pituitary-gonadal axis in premenopausal women are unknown. Patients treated with lovastatin who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should also be exercised if an HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered to patients also receiving other drugs (e.g., spironolactone, cimetidine) that may decrease the levels or activity of endogenous steroid hormones.

CNS toxicity - Lovastatin produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). Vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis were also seen in dogs treated for 14 weeks at 180 mg/kg/day, a dose which resulted in a mean plasma drug level (Cmax) similar to that seen with the 60 mg/kg/day dose.

CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels, were seen in dogs treated with lovastatin at a dose of 180 mg/kg/day, a dose which produced plasma drug levels (Cmax) which were about 30 times higher than the mean values in humans taking 80 mg/day.

Similar optic nerve and CNS vascular lesions have been observed with other drugs of this class.

Cataracts were seen in dogs treated with lovastatin for 11 and 28 weeks at 180 mg/kg/day and 1 year at 60mg/kg/day.

Information for Patients

Patients should be advised of the following:

  • to report promptly unexplained muscle pain, tenderness, or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Advicor (see WARNINGS, Myopathy/Rhabdomyolysis);
  • to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice (see WARNINGS, Liver Dysfunction);
  • to take Advicor at bedtime, with a low-fat snack. Administration on an empty stomach is not recommended;
  • to carefully follow the prescribed dosing regimen (see DOSAGE AND ADMINISTRATION);
  • that flushing is a common side effect of niacin therapy that usually subsides after several weeks of consistent niacin use. Flushing may last for several hours after dosing, may vary in severity, and will, by taking Advicor at bedtime, most likely occur during sleep. If awakened by flushing, especially if taking antihypertensives, rise slowly to minimize the potential for dizziness and/or syncope;
  • that taking aspirin (up to approximately 30 minutes before taking Advicor) may minimize flushing;
  • to avoid ingestion of alcohol, hot beverages and spicy foods around the time of Advicor administration, to minimize flushing;
  • should not be administered with grapefruit juice;
  • that if Advicor therapy is discontinued for an extended length of time, their physician should be contacted prior to re-starting therapy; re-titration is recommended (see DOSAGE AND ADMINISTRATION);
  • to notify their physician if they are taking vitamins or other nutritional supplements containing niacin or related compounds such as nicotinamide (see Drug Interactions);
  • to notify their physician if symptoms of dizziness occur;
  • if diabetic, to notify their physician of changes in blood glucose;
  • that Advicor tablets should not be broken, crushed, or chewed, but should be swallowed whole.

Drug Interactions

Niacin

Antihypertensive Therapy - Niacin may potentiate the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension.

Aspirin - Concomitant aspirin may decrease the metabolic clearance of niacin. The clinical relevance of this finding is unclear.

Bile Acid Sequestrants - An in vitro study was carried out investigating the niacin-binding capacity of colestipol and cholestyramine. About 98% of available niacin was bound to colestipol, with 10 to 30% binding to cholestyramine. These results suggest that 4 to 6 hours, or as great an interval as possible, should elapse between the ingestion of bile acid-binding resins and the administration of Advicor.

Other - Concomitant alcohol or hot drinks may increase the side effects of flushing and pruritus and should be avoided around the time of Advicor ingestion. Vitamins or other nutritional supplements containing large doses of niacin or related compounds such as nicotinamide may potentiate the adverse effects of Advicor.

Lovastatin

Lovastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4. Strong inhibitors of CYP3A4 (e.g., itraconazole, ketoconazole, posaconazole, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, and erythromycin), and large quantities of grapefruit juice (>1 quart daily) increase the risk of myopathy by reducing the elimination of lovastatin (see WARNINGS, Myopathy/Rhabdomyolysis).

In vitro studies have demonstrated that voriconazole inhibits the metabolism of lovastatin. Adjustment of the lovastatin dose may be needed to reduce the risk of myopathy, including rhabdomyolysis, if voriconazole must be used concomitantly with lovastatin.

Interactions With Lipid-Lowering Drugs That Can Cause Myopathy When Given Alone

The risk of myopathy is also increased by the following lipid-lowering drugs that are not strong CYP3A4 inhibitors, but which can cause myopathy when given alone (see WARNINGS, Myopathy/Rhabdomyolysis).

Gemfibrozil

Other fibrates

Other Drug Interactions

Cyclosporine: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of cyclosporine (see WARNINGS, Myopathy/Rhabdomyolysis).

Danazol, Diltiazem, or Verapamil: The risk of myopathy/rhabdomyolysis is increased by concomitant administration of danazol, diltiazem, or verapamil particularly with higher doses of lovastatin (see WARNINGS, Myopathy/Rhabdomyolysis and CLINICAL PHARMACOLOGY, Pharmacokinetics).

Amiodarone: The risk of myopathy/rhabdomyolysis is increased when amiodarone is used concomitantly with a closely related member of the HMGCoA reductase inhibitor class (see WARNINGS, Myopathy/Rhabdomyolysis).

Coumarin Anticoagulants - In a small clinical study in which lovastatin was administered to warfarin-treated patients, no effect on PT was detected. However, another HMG-CoA reductase inhibitor has been found to produce a less than two seconds increase in PT in healthy volunteers receiving low doses of warfarin. Also, bleeding and/or increased PT have been reported in a few patients taking coumarin anticoagulants concomitantly with lovastatin. It is recommended that in patients taking anticoagulants, PT be determined before starting Advicor and frequently enough during early therapy to insure that no significant alteration of PT occurs. Once a stable PT has been documented, PT can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of Advicor is changed, the same procedure should be repeated.

Colchicine - Cases of myopathy, including rhabdomyolysis, have been reported with lovastatin coadministered with colchicine.

Ranolazine - The risk of myopathy, including rhabdomyolysis, may be increased by concomitant administration of ranolazine.

Propranolol - In normal volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interaction with concomitant administration of single doses of lovastatin and propranolol.

Digoxin - In patients with hypercholesterolemia, concomitant administration of lovastatin and digoxin resulted in no effect on digoxin plasma concentrations.

Oral Hypoglycemic Agents - In pharmacokinetic studies of lovastatin in hypercholesterolemic, non-insulin dependent diabetic patients, there was no drug interaction with glipizide or with chlorpropamide.

Drug/Laboratory Test Interactions

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been conducted with Advicor regarding carcinogenesis, mutagenesis, or impairment of fertility.

Niacin

Niacin, administered to mice for a lifetime as a 1% solution in drinking water, was not carcinogenic. The mice in this study received approximately 6 to 8 times a human dose of 3000 mg/day as determined on a mg/m2 basis. Niacin was negative for mutagenicity in the Ames test. No studies on impairment of fertility have been performed.

Lovastatin

In a 21-month carcinogenic study in mice, there was a statistically significant increase in the incidence of hepatocellular carcinomas and adenomas in both males and females at 500 mg/kg/day. This dose produced a total plasma drug exposure 3 to 4 times that of humans given the highest recommended dose of lovastatin (drug exposure was measured as total HMG-CoA reductase inhibitory activity in extracted plasma). Tumor increases were not seen at 20 and 100 mg/kg/day, doses that produced drug exposures of 0.3 to 2 times that of humans at the 80 mg/day dose. A statistically significant increase in pulmonary adenomas was seen in female mice at approximately 4 times the human drug exposure. (Although mice were given 300 times the human dose on a mg/kg body weight basis, plasma levels of total inhibitory activity were only 4 times higher in mice than in humans given 80 mg of lovastatin.)

There was an increase in incidence of papilloma in the non-glandular mucosa of the stomach of mice beginning at exposures of 1 to 2 times that of humans. The glandular mucosa was not affected. The human stomach contains only glandular mucosa.

In a 24-month carcinogenicity study in rats, there was a positive dose-response relationship for hepatocellular carcinogenicity in males at drug exposures between 2 to 7 times that of human exposure at 80 mg/day (doses in rats were 5, 30, and 180 mg/kg/day).

An increased incidence of thyroid neoplasms in rats appears to be a response that has been seen with other HMG-CoA reductase inhibitors.

A drug in this class chemically similar to lovastatin was administered to mice for 72 weeks at 25, 100, and 400 mg/kg body weight, which resulted in mean serum drug levels approximately 3, 15, and 33 times higher than the mean human serum drug concentration (as total inhibitory activity) after a 40 mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males, with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls.

No evidence of mutagenicity was observed in a microbial mutagen test using mutant strains of Salmonella typhimurium with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in an in vitro alkaline elution assay using rat or mouse hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.

Drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation were seen in dogs starting at 20 mg/kg/day. Similar findings were seen with another drug in this class. No drug-related effects on fertility were found in studies with lovastatin in rats. However, in studies with a similar drug in this class, there was decreased fertility in male rats treated for 34 weeks at 25 mg/kg body weight, although this effect was not observed in a subsequent fertility study when this same dose was administered for 11 weeks (the entire cycle of spermatogenesis, including epididymal maturation). In rats treated with this same reductase inhibitor at 180 mg/kg/day, seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. No microscopic changes were observed in the testes from rats of either study. The clinical significance of these findings is unclear.

Pregnancy

Pregnancy Category X

See CONTRAINDICATIONS.

Advicor should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazard. Safety in pregnant women has not been established and there is no apparent benefit to therapy with Advicor during pregnancy (see CONTRAINDICATIONS). Treatment should be immediately discontinued as soon as pregnancy is recognized.

Niacin

Animal reproduction studies have not been conducted with niacin or with Advicor. It is also not known whether niacin at doses typically used for lipid disorders can cause fetal harm when administered to pregnant women or whether it can affect reproductive capacity. If a woman receiving niacin or Advicor for primary hypercholesterolemia becomes pregnant, the drug should be discontinued.

Lovastatin

Rare reports of congenital anomalies have been received following intrauterine exposure to HMG-CoA reductase inhibitors. In a review5 of approximately 100 prospectively followed pregnancies in women exposed to lovastatin or another structurally related HMG-CoA reductase inhibitor, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a 3- to 4-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Lovastatin has been shown to produce skeletal malformations at plasma levels 40 times the human exposure (for mouse fetus) and 80 times the human exposure (for rat fetus) based on mg/m2 surface area (doses were 800 mg/kg/day). No drug-induced changes were seen in either species at multiples of 8 times (rat) or 4 times (mouse) based on surface area. No evidence of malformations was noted in rabbits at exposures up to 3 times the human exposure (dose of 15 mg/kg/day, highest tolerated dose).

Labor and Delivery

No studies have been conducted on the effect of Advicor, niacin or lovastatin on the mother or the fetus during labor or delivery, on the duration of labor or delivery, or on the growth, development, and functional maturation of the child.

Nursing Mothers

No studies have been conducted with Advicor in nursing mothers.

Because of the potential for serious adverse reactions in nursing infants from lipid-altering doses of niacin and lovastatin (see CONTRAINDICATIONS), Advicor should not be taken while a woman is breastfeeding.

Niacin has been reported to be excreted in human milk. It is not known whether lovastatin is excreted in human milk. A small amount of another drug in this class is excreted in human breast milk.

Pediatric Use

No studies in patients under 18 years-of-age have been conducted with Advicor. Because pediatric patients are not likely to benefit from cholesterol lowering for at least a decade and because experience with this drug or its active ingredients is limited, treatment of pediatric patients with Advicor is not recommended at this time.

Geriatric Use

Of the 214 patients who received Advicor in double-blind clinical studies, 37.4% were 65 years-of-age and older, and of the 814 patients who received Advicor in open-label clinical studies, 36.2% were 65 years-of-age and older. Responses in LDL-C, HDL-C, and TG were similar in geriatric patients. No overall differences in the percentage of patients with adverse events were observed between older and younger patients. No overall differences were observed in selected chemistry values between the two groups except for amylase which was higher in older patients.

Adverse Reactions

Overview

In controlled clinical studies, 40/214 (19%) of patients randomized to Advicor discontinued therapy prior to study completion. Of the 214 patients enrolled 18 (8%) discontinued due to flushing. In the same controlled studies, 9/94 (10%) of patients randomized to lovastatin and 19/92 (21%) of patients randomized to NIASPAN also discontinued treatment prior to study completion secondary to adverse events. Flushing episodes (i.e., warmth, redness, itching and/or tingling) were the most common treatment-emergent adverse events, and occurred in 53% to 83% of patients treated with Advicor. Spontaneous reports with NIASPAN and clinical studies with Advicor suggest that flushing may also be accompanied by symptoms of dizziness or syncope, tachycardia, palpitations, shortness of breath, sweating, burning sensation/skin burning sensation, chills, and/or edema.

Adverse Reactions Information

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. The adverse reaction information from clinical studies does, however provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

The data described in this section reflect the exposure to Advicor in two double-blind, controlled clinical studies of 400 patients. The population was 28 to 86 years-of-age, 54% male, 85% Caucasian, 9% Black, and 7% Other, and had mixed dyslipidemia.

In addition to flushing, other adverse events occurring in 5% or greater of patients treated with Advicor are shown in Table 10 below.

Table 10. Treatment-Emergent Adverse Events in ≥ 5% of Patients (Events Irrespective of Causality; Data from Controlled, Double-Blind Studies)
Adverse Event Advicor NIASPAN Lovastatin
       
Total Number of Patients 214 92 94
       
Cardiovascular 163 (76%) 66 (72%) 24 (26%)
Flushing 152 (71%) 60 (65%) 17 (18%)
       
Body as a Whole 104 (49%) 50 (54%) 42 (45%)
Asthenia 10 ( 5%) 6 ( 7%) 5 ( 5%)
Flu Syndrome 12 ( 6%) 7 ( 8%) 4 ( 4%)
Headache 20 ( 9%) 12 (13%) 5 ( 5%)
Infection 43 (20%) 14 (15%) 19 (20%)
Pain 18 ( 8%) 3 ( 3%) 9 (10%)
Pain, Abdominal 9 ( 4%) 1 ( 1%) 6 ( 6%)
Pain, Back 10 ( 5%) 5 ( 5%) 5 ( 5%)
       
Digestive System 51 (24%) 26 (28%) 16 (17%)
Diarrhea 13 ( 6%) 8 ( 9%) 2 ( 2%)
Dyspepsia 6 ( 3%) 5 ( 5%) 4 ( 4%)
Nausea 14 ( 7%) 11 (12%) 2 ( 2%)
Vomiting 7 ( 3%) 5 ( 5%) 0
       
Metabolic and Nutrit. System 37 (17%) 18 (20%) 13 (14%)
Hyperglycemia 8 ( 4%) 6 ( 7%) 6 ( 6%)
       
Musculoskeletal System 19 ( 9%) 9 (10%) 17 (18%)
Myalgia 6 ( 3%) 5 ( 5%) 8 ( 9%)
       
Skin and Appendages 38 (18%) 19 (21%) 11 (12%)
Pruritus 14 ( 7%) 7 ( 8%) 3 ( 3%)
Rash 11 ( 5%) 11 (12%) 3 ( 3%)
Note: Percentages are calculated from the total number of patients in each column.

See also the full prescribing information for niacin extended release (Niaspan) and lovastatin products.

The following adverse events have also been reported with niacin, lovastatin, and/or other HMG-CoA reductase inhibitors, but not necessarily with Advicor, either during clinical studies or in routine patient management.

Body as a Whole: chest pain; abdominal pain; edema; chills; malaise
Cardiovascular: atrial fibrillation; tachycardia; palpitations, and other cardiac arrhythmias; postural hypotension, orthostasis; hypotension; syncope
Eye: toxic amblyopia; cystoid macular edema; ophthalmoplegia; eye irritation, blurred vision, progression of cataracts
Gastrointestinal: activation of peptic ulcers and peptic ulceration; dyspepsia; vomiting; anorexia; constipation; flatulence, pancreatitis; hepatitis; fatty change in liver; jaundice; and rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma, eructation, fatal and non-fatal hepatic failure
Metabolic: gout, decreased glucose tolerance
Musculoskeletal: muscle cramps; myopathy; rhabdomyolysis; arthralgia, myalgia.
There have been rare reports of immune-mediated necrotizing myopathy with statin use (see WARNINGS).
Nervous: dizziness; insomnia; dry mouth; paresthesia; anxiety; tremor; vertigo; peripheral neuropathy; psychic disturbances; dysfunction of certain cranial nerves, nervousness, burning sensation/skin burning sensation, peripheral nerve palsy
Psychiatric depression
Skin: hyper-pigmentation; acanthosis nigricans; urticaria; alopecia; dry skin; sweating; and a variety of skin changes (e.g., nodules, discoloration, dryness of mucous membranes, changes to hair/nails), vesiculobullous rash, maculopapular rash
Respiratory: dyspnea; rhinitis
Urogenital: gynecomastia; loss of libido; erectile dysfunction
Hypersensitivity reactions: An apparent hypersensitivity syndrome has been reported rarely, which has included one or more of the following features: anaphylaxis, angioedema, tongue edema, larynx edema, face edema, peripheral edema, laryngismus, lupus erythematous-like syndrome, polymyalgia rheumatica, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome, dermatomyositis
Other: migraine

There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

Clinical Laboratory Abnormalities

Chemistry

Elevations in serum transaminases (see WARNINGS - Liver Dysfunction), CPK and fasting glucose, and reductions in phosphorus. Niacin extended-release tablets have been associated with slight elevations in LDH, uric acid, total bilirubin, amylase and creatine kinase. Lovastatin and/or HMG-CoA reductase inhibitors have been associated with elevations in alkaline phosphatase, γ-glutamyl transpeptidase and bilirubin, and thyroid function abnormalities.

Hematology

Niacin extended-release tablets have been associated with slight reductions in platelet counts and prolongation in PT (see WARNINGS).

How is Advicor Supplied

Advicor is an unscored capsule-shaped tablet containing either 500, 750, or 1000 mg of extended-release niacin, and 20 mg of immediate-release lovastatin (Advicor 500 mg/20 mg, 750 mg/20 mg, 1000 mg/20 mg), or 1000 mg of extended-release niacin and 40 mg of immediate-release lovastatin (Advicor 1000 mg/40 mg). Tablets are color-coated and printed with the “a” logo and a code number specific to the tablet strength on the same side. Advicor 500 mg/20 mg tablets are light yellow, code “502”. Advicor 750 mg/20 mg tablets are light orange, code “752”. Advicor 1000 mg/20 mg tablets are dark pink/light purple, code “1002”. Advicor 1000 mg/40 mg tablets are reddish brown, code “1004.” Tablets are supplied in bottles of 90 tablets as shown below.

500 mg/20 mg tablets: bottles of 90 - NDC# 0074-3005-90

750 mg/20 mg tablets: bottles of 90 - NDC# 0074-3072-90

1000 mg/20 mg tablets: bottles of 90 - NDC# 0074-3007-90

1000 mg/40 mg tablets: bottles of 90 - NDC# 0074-3010-90

Store at room temperature (20° to 25°C or 68° to 77°F).

NIASPAN is a registered trademark of AbbVie Inc., and Mevacor is a registered trademark of Merck & Co., Inc.

References

  1. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-2497.
  2. Downs JR, et al. JAMA 1998; 279:1615-1622.
  3. Bradford RH, et al. Arch Intern Med 1991;151:43-49.
  4. Bradford RH, et al. Am J Cardiol 1994; 74:667-673.
  5. Manson JM, et al. Reprod Toxicol 1996; 10(6): 439-446.

Manufactured by AbbVie LTD, Barceloneta, PR 00617
for AbbVie Inc., North Chicago, IL 60064, U.S.A.

© 2013 AbbVie Inc.



03-A745 February, 2013

NDC 0074–3005–90

Advicor®

Niacin Extended-Release/Lovastatin

500 mg / 20 mg

90 Tablets

Rx only abbvie

NDC 0074–3072–90

Advicor®

Niacin Extended-Release/Lovastatin

750 mg / 20 mg

90 Tablets

Rx only abbvie

NDC 0074–3007–90

Advicor®

Niacin Extended-Release/Lovastatin

1000 mg / 20 mg

90 Tablets

Rx only abbvie

NDC 0074–3010–90

Advicor®

Niacin Extended-Release/Lovastatin

1000 mg / 40 mg

90 Tablets

Rx only abbvie

Advicor 
niacin and lovastatin tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-3005
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIACIN (NIACIN) NIACIN 500 mg
LOVASTATIN (LOVASTATIN) LOVASTATIN 20 mg
Inactive Ingredients
Ingredient Name Strength
TITANIUM DIOXIDE  
POLYSORBATE 80  
FERRIC OXIDE RED  
FERRIC OXIDE YELLOW  
HYPROMELLOSES  
STEARIC ACID  
POLYETHYLENE GLYCOLS  
POVIDONES  
Product Characteristics
Color YELLOW (LIGHT YELLOW) Score no score
Shape OVAL (OVAL) Size 17mm
Flavor Imprint Code A;502
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-3005-90 90 TABLET, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021249 12/17/2001 03/31/2018
Advicor 
niacin and lovastatin tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-3072
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIACIN (NIACIN) NIACIN 750 mg
LOVASTATIN (LOVASTATIN) LOVASTATIN 20 mg
Inactive Ingredients
Ingredient Name Strength
POLYSORBATE 80  
FD&C YELLOW NO. 6  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
POVIDONES  
STEARIC ACID  
TITANIUM DIOXIDE  
Product Characteristics
Color ORANGE (LIGHT ORANGE) Score no score
Shape OVAL (OVAL) Size 19mm
Flavor Imprint Code A;752
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-3072-90 90 TABLET, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021249 12/17/2001 04/30/2017
Advicor 
niacin and lovastatin tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-3007
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIACIN (NIACIN) NIACIN 1000 mg
LOVASTATIN (LOVASTATIN) LOVASTATIN 20 mg
Inactive Ingredients
Ingredient Name Strength
STEARIC ACID  
POLYSORBATE 80  
FERRIC OXIDE RED  
FERRIC OXIDE YELLOW  
FERROSOFERRIC OXIDE  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
POVIDONES  
TITANIUM DIOXIDE  
Product Characteristics
Color PINK (DARK PINK/LIGHT PURPLE) Score no score
Shape OVAL (OVAL) Size 19mm
Flavor Imprint Code A;1002
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-3007-90 90 TABLET, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021249 12/17/2001 11/30/2017
Advicor 
niacin and lovastatin tablet, extended release
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0074-3010
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
NIACIN (NIACIN) NIACIN 1000 mg
LOVASTATIN (LOVASTATIN) LOVASTATIN 40 mg
Inactive Ingredients
Ingredient Name Strength
STEARIC ACID  
TITANIUM DIOXIDE  
FERRIC OXIDE RED  
HYPROMELLOSES  
POLYETHYLENE GLYCOLS  
POVIDONES  
POLYSORBATE 80  
Product Characteristics
Color BROWN (REDDISH BROWN) Score no score
Shape OVAL (OVAL) Size 19mm
Flavor Imprint Code A;1004
Contains     
Packaging
# Item Code Package Description
1 NDC:0074-3010-90 90 TABLET, EXTENDED RELEASE in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA021249 12/17/2001 01/31/2018
Labeler - AbbVie Inc. (078458370)
Revised: 03/2017   AbbVie Inc.

For the Consumer

Applies to lovastatin / niacin: oral tablet, oral tablet extended release

Along with its needed effects, lovastatin / niacin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking lovastatin / niacin:

More common
  • Cough or hoarseness
  • feeling of warmth
  • fever or chills
  • lower back or side pain
  • pain
  • painful or difficult urination
  • redness, itching, or tingling of the face, neck, arms, and occasionally, upper chest
Less common
  • Abdominal or stomach pain
  • blurred vision
  • cramping pain or stiffness
  • difficulty moving
  • dry mouth
  • dry skin
  • fruit-like breath odor
  • increased hunger
  • increased thirst
  • increased urination
  • joint pain
  • muscle aches, weakness, tenderness, or pain
  • nausea
  • swollen joints
  • unexplained weight loss
  • unusual tiredness or weakness
  • vomiting
Rare
  • Dark-colored urine
  • muscle cramps, pain, spasm, or stiffness

Some side effects of lovastatin / niacin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
  • general feeling of discomfort or illness
  • headache
  • itching skin
  • loss of appetite
  • nausea
  • rash
  • runny nose
  • shivering
  • shortness of breath
  • sore throat
  • sweating
  • trouble sleeping
Less common
  • Acid or sour stomach
  • belching
  • heartburn
  • indigestion
  • lack or loss of strength
  • stomach discomfort or upset

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