Lantus: Introduction

For many diabetics, each day is structured around the administration of multiple insulin injections to control their blood sugar levels. Now a new form of insulin will soon be available that may make life easier for many diabetics who require these daily injections. Called Lantus, it is the first once-a-day manmade insulin injection to be approved by the FDA. Aventis Pharmaceuticals, the manufacturer of Lantus, received FDA approval for the drug on April 24, 2000.

Lantus (insulin glargine [rDNA origin] injection) is indicated for the treatment of adults and children with type 1 diabetes mellitus, and adults with type 2 diabetes mellitus who require long-acting insulin for control of hyperglycemia. Just one injection a day provides control of blood sugar (glucose) levels for a full 24 hours.

Lantus: How Does It Work?

Lantus is a “recombinant human insulin analog” — a manmade insulin that closely mimics human insulin. The chemical structure of Lantus regulates its release from the tissue under the skin into the bloodstream, providing a glucose-lowering effect that lasts for 24 hours. The longer duration of action of Lantus is directly related to its slower rate of absorption.

Lantus: Clinical Study Results

Several controlled clinical trials showed that Lantus was as effective as human insulin for controlling blood sugar levels. Moreover, the incidence of hypoglycemia – low blood sugar – was lower in patients who used Lantus than in those who took regular insulin. Lantus was effective in adults and children with type 1 (insulin-dependent) diabetes, as well as adults with type 2 diabetes who need insulin injections to control their blood sugar.

Lantus: What You Should Know

Human insulin therapy may be associated with hypoglycemia, worsening of diabetic retinopathy (a disorder of the retina of the eye), skin reactions (such as injection-site reaction, itching, and rash), allergic reactions, and retention of fluid. Hypoglycemia is the most common adverse effect of insulins, including Lantus. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes.

Any change in insulin should be made cautiously and only under medical supervision. In clinical studies of adult patients, there was a higher incidence of injection-site pain in patients who used Lantus than in those who took regular insulin. However, pain at the injection site was usually mild and did not result in discontinuation of therapy.

Lantus must not be diluted or mixed with any other insulin or solution, as it may result in a delayed onset of action. You should inform your health care provider about any other medications you may be taking, since they may alter the way Lantus works in your body.

Effexor: Introduction

The drug Effexor (venlafaxine hydrochloride) was approved by the FDA in 1993 for the treatment of depression and anxiety. An extended-release once-daily dosing preparation, Effexor XR, received marketing clearance in 1997. Now Effexor XR is showing promise for ameliorating the symptoms of another disorder: diabetic neuropathy. The results of the study were reported at the 60th annual meeting of the American Diabetes Association in June 2000.

In doses ranging from 150-225 mg/day, Effexor XR had significantly higher analgesic response rates compared to placebo. The drug is manufactured by Wyeth-Ayerst Laboratories, a division of American Home Products.

Effexor: How It Works

Effexor is a serotonin and norepinephrine reuptake inhibitor. Both serotonin and norepinephrine are involved not only in mediation of mood but also perception of pain.

Effexor: Clinical Study Results

The efficacy, safety, and tolerability of Effexor XR as a treatment for painful diabetic neuropathy were assessed in a double-blind, placebo-controlled, parallel-group multicenter study. A total of 244 patients age 18 or older with type 1 or type 2 diabetes were randomly assigned to receive treatment with Effexor XR 75 mg, 150-225 mg, or placebo for up to 6 weeks. Primary efficacy was measured by patient self-rating assessments of pain intensity and pain relief using a Visual Analog Scale (VAS-PI and VAS-PR). Secondary efficacy was determined by patient self-ratings of pain relief on the Patient Global Rating of Pain Relief scale, and by investigator-rated assessments of pain on the Clinical Global Impressions Severity of Illness (CGI-S) and Clinical Global Impressions Global Improvement (CGI-I) scales.

On both primary outcome measures, Effexor XR 150-225 mg produced significantly greater pain relief at all evaluations compared with placebo. Effexor XR 75 mg produced significant pain relief, compared with placebo, on the VAS-PR scale at weeks 2, 3, and 5. Additionally, by week 6, 56% of patients treated with Effexor XR 150-225 mg experienced significantly lowered pain intensity, compared with 39% treated with Effexor XR 75 mg and 34% given a placebo.

On all secondary measures, similar statistical superiority over placebo was demonstrated for Effexor XR 150-225 mg. Since the presence of major depressive disorder was an exclusion criterion in the study, symptom improvement was attributed to analgesic, rather than an antidepressant, effect.

Effexor: Adverse Events

The most common adverse event associated with Effexor XR was nausea. Other side effects that may occur with use of Effexor XR include insomnia and nervousness, anorexia and weight loss, and sustained hypertension. Because Effexor XR may interact with monoamine oxidase inhibitors, it is recommended that it not be used in combination with these agents, or within at least 14 days of discontinuing treatment with an MAO inhibitor.

Hypertension and Diabetes Risk Factors in the African American Population
The high prevalence of hypertension and diabetes in African Americans increases their risk for CHD. The presence of cholesterol abnormalities (i.e., increased LDL, triglycerides, and decreased HDL) in conjunction with these two major risk factors puts this population at an even greater risk for cardiovascular morbidity and mortality. It is imperative that pharmacists recognize this population as one requiring special considerations with regard to monitoring and counseling. Hypertension appears to increase with the prevalence of certain lifestyles. In the rural South (as well as in other areas), certain cultural food preferences still exist. For example, chitterlings, salt back, pickled pig parts, fat back, sweet potato pie, and boiled peanuts are major components of many African American diets. Many of these foods are high in fat and sodium, and low in potassium. Diets high in fried foods and low in fruits, vegetables, and grains pose significant challenges for the patient with dyslipidemia, making lifestyle modifications more critical. The assistance of a dietitian may be particularly useful for recommending low-fat, low-sodium alternatives to the patient.

To prevent hypertension, African Americans should increase consumption of high-potassium foods (such as fresh fruits and vegetables), use low-fat dairy products, and avoid salt. The Dietary Approaches to Stop Hypertension (DASH) diet is particularly effective in significantly lowering high blood pressure in African Americans. This diet is low in cholesterol, high in dietary fiber, potassium, calcium, and magnesium, and moderately high in protein, and has been shown to lower blood pressure even when an individual’s weight and salt intake remained constant. One major obstacle facing many African Americans in the treatment of hypertension, is the cost of medications. Many of the newer medications are more effective and have fewer side effects than older medications, but they are costly. In addition, many African Americans do not receive proper medical care until hypertension has been present for some time. This results in otherwise avoidable damage to the kidneys and other organs. It may also account for the high rate of hypertension-related morbidity and mortality that exists among African Americans.

It should also be taken into consideration that African Americans tend to respond differently than other populations to treatment for high blood pressure. Because African Americans experience higher rates of diabetes, renal insufficiency and heart failure, they may benefit more from aggressive treatments to lower blood pressure.

Conclusion
Dyslipidemia is a major risk factor in the development of coronary heart disease. This risk factor, as well as other risk factors, can be altered through pharmacologic, dietary and other lifestyle modifications. Cultural norms affecting health among African Americans do exist and should not be overlooked by healthcare providers. Increased awareness by the pharmacist and the use of culturally sensitive information and materials can greatly enhance patient understanding and adherence to the prescribed regimen.
Pharmacists have a responsibility to assist in the management of lipid disorders. This can be accomplished by developing individual or collaborative practices in various healthcare settings. Pharmacists interested in strengthening their skills in this area can enroll in courses offered by several organizations.

Both epidemiologic and clinical trials have documented the prevalence of lipid disorders, and have proven that elevated levels of low-density lipoprotein (LDL) cholesterol and decreased levels of high-density lipoprotein (HDL) are associated with an increased risk of CHD. (Pharmacists should be aware that certain diseases and medications are also capable of affecting cholesterol levels. Therefore, patient medication profiles and medical histories should be reviewed thoroughly to rule out these possible secondary causes of dyslipidemia.) In addition to elevated cholesterol, other risk factors for CHD have been identified:

• Age: Male 45 years or older; female 55 years or older, or experiencing premature menopause without estrogen replacement therapy
• Family history: History of premature CHD (definite myocardial infarction or sudden death before age 55 in father or other male first-degree relative, or before age 65 in mother or other female first-degree relative)
• Current cigarette smoking
• Hypertension (blood pressure 140/90 mmHg or greater) or taking antihypertensive medicine
• Diabetes mellitus

Management of Elevated Cholesterol
The National Cholesterol Education Program (NCEP) of the National Heart, Lung and Blood Institute (NHLBI) has established guidelines for the prevention and treatment of lipid disorders. According to the NCEP guidelines, all patients at least 20 years of age should have an initial cholesterol measurement. It is recommended that the initial laboratory test measure both total and HDL cholesterol. The American Diabetes Association (ADA) recommends that diabetic patients receive a complete lipid profile (i.e., LDL, HDL and triglycerides) annually. Further evaluation of the patient is based on the results of these initial tests. The goals of lipid-lowering interventions vary depending on whether the focus is primary or secondary prevention of CHD. In primary prevention the goal is to prevent the onset of CHD; secondary prevention focuses on avoiding further CHD events. Treatment should be modeled after NCEP recommendations. These guidelines include nonpharmacologic, lifestyle modifications (e.g., diet, exercise, smoking cessation), and pharmacologic measures. Table 1 outlines the LDL treatment goals based on the number of CHD risk factors present.

Lifestyle Modification: Dietary therapy is the first line of treatment for elevated cholesterol levels. NCEP recognizes dietary modification as the cornerstone in the management of dyslipidemia. The general goal of dietary therapy is to reduce elevated serum cholesterol while maintaining a nutritionally appropriate eating pattern. A reduction in saturated fat and cholesterol in the diet, as well as regular physical activity, are two important lifestyle changes that pharmacists must emphasize to patients. Dietary therapy is a two-step process. Step I begins the process of reducing intake of saturated fat and cholesterol. The diet should involve an intake of 10% of total calories from saturated fat, 30% or less of calories from total fat, and 300 mg or less of cholesterol per day (Table 2). If the goals of therapy are not achieved with Step I, patients should be advanced to the Step II diet. Step II requires further reduction in saturated fat and cholesterol. For this step, a registered dietitian should assist with management.

Both physical activity and weight reduction are considered essential components in the nonpharmacologic management of elevated serum cholesterol. A program of physical activity for at least 20 minutes three times weekly provides significant cardiovascular benefit. The benefits of physical activity include an increase in HDL and a decrease in weight, especially for obese and overweight patients. It may also lead to a reduction in triglyceride levels. Patients should be advised to consult their physician prior to initiating an exercise program.
Smoking cessation should also be encouraged. Pharmacists should have information available, and be able to direct patients to local smoking cessation programs. They should be knowledgeable about the various smoking cessation aids available (e.g., nicotine gum and patches).

Pharmocologic Measures: The goal of drug therapy is to reduce the LDL cholesterol to below 160 mg/dL or to below 130 mg/dL if two other risk factors are present. Drug therapy is considered for the adult patient who has an LDL cholesterol level of 190 mg/dL or greater without two other risk factors; or 160 mg/dL or greater with two other risk factors. Table 3 outlines the NCEP guidelines for treatment, and Table 4 summarizes patient counseling information specific to each lipid-lowering agent available.

An international team of researchers for the Heart Outcomes Prevention Evaluation Study looked at the effectiveness of the ACE inhibitor ramipril (Altace) in preventing heart attack, stroke, and cardiovascular death among 3,577 diabetics from 19 countries in North and South America and Europe. Participants, who were at least 55 years old and had at least one cardiovascular risk factor, were randomly assigned to take either 10 mg/day of ramipril or placebo, along with 400 IU/day of vitamin E or placebo. Evaluation took place every six months for four and one-half years.

When the researchers combined the outcomes for heart attack, stroke, and cardiovascular death, patients taking ramipril were 25 percent less likely than those taking placebo to experience any of these events. Significant effects for ramipril were seen after two years and maintained until the end of the study. These effects were still significant after accounting for the lower blood pressure caused by taking ramipril.

Whether patients had type 1 or type 2 diabetes made no difference in ramipril’s effect, nor did how well their diabetes was controlled, what treatment they received for their diabetes, or whether they had hypertension or a history of cardiovascular disease.

Ramipril (Altace) also lowered risk for kidney damage, even among those with microalbuminuria, the spilling of protein in the urine that indicates early kidney problems.

The researchers suggest that ramipril’s effects on people with diabetes may be due to a protective effect on artery walls, allowing vessels to dilate more. They conclude that ramipril should be added to the list of strategies that can help prevent cardiovascular and kidney disease among diabetics, including lowering blood pressure and cholesterol, controlling blood sugar, quitting smoking, and taking aspirin daily.