Statin therapy

Which administration information will a nurse provide to a patient who is newly prescribed immediate-release lovastatin 20 mg?

Take it in the evening with a meal. Immediate-release lovastatin must be taken with an evening meal. The timing and conditions of the statin administration are important to ensure the patient receives maximal lipid-lowering effects.

Which parameters are expected to decrease with statins?

Triglycerides total cholesterol apolipoprotein B-100 Low density lipoprotein (LDL) cholesterol

These drugs are referred to as statins because of the shared ending of their generic names. There are currently seven statin drugs available:

atorvastatin fluvastatin lovastatin pitavastatin pravastatin rosuvastatin simvastatin

Therapeutically Equivalent Doses

atorvastatin 10 mg fluvastatin 80 mg lovastatin 40 mg pitavastatin 2 mg pravastatin 40 mg rosuvastatin 5 mg simvastatin 20 mg

When is atorvastatin expected to achieve its peak concentration?

1 to 2 hrs

Atorvastatin peak of concentration

1-2hrs

Pitavastatin adult dosage

1-4 mg/day May be taken without regard to meals at any point during the day.

simvastatin peak concentration

1.3 to 2.4 hrs

Atorvastatin adult dosage

10-80 mg/day May be taken without regard to meals at any point in the day.

Simvastatin adult dosage

10-80 mg/day Should be administered in the evening without regard to meals. The 80-mg dose is restricted to patients who have been taking simvastatin 80 mg for 1 year or longer without evidence of muscle toxicity.

Lovastatin adult dosage

10-80 mg/day (immediate release)20-60 mg/day (extended release) The immediate release must be taken with an evening meal. The extended release should be given in the evening at bedtime.

Atorvastatin Elimination half-life

14-30hrs

simvastatin elimination half-life

2-3 hrs

Fluvastatin adult dosage

20-80 mg/day (both immediate and extended release) May be taken without regard to food. Only the extended-release formulation can be taken at any point during the day; the immediate-release must be taken at bedtime.

Simvastatin onset of action

3 days

Pravastatin adult dosage

40-80 mg/day May be taken without regard to meals at any point during the day.

Rosuvastatin adult dosage

5-40 mg/day May be taken without regard to meals at any point during the day.

Which patients would a nurse determine can safely receive treatment with a statin in the absence of any other factors?

A 48-year-old patient with hyperthyroidism A 55-year-old patient with type 2 diabetes mellitus

An obese 84-year-old patient is taking simvastatin 10 mg PO each evening. In addition to dyslipidemia, the patient has hypertension, diabetes, and hypothyroidism. Which factors increase this patient's risk for rhabdomyolysis?

Advanced age Hypothyroidism

Distribution

All statins are highly protein bound (e.g., 95% or higher) except for pravastatin, which has protein binding reported to be between 43% and 55%.

A 51-year-old male patient has been prescribed lovastatin 40 mg PO each evening to help lower his low-density lipoprotein (LDL) cholesterol. In addition to lovastatin, this patient also takes pantoprazole for gastroesophageal reflux disease (GERD), amiodarone for atrial fibrillation, tamsulosin for benign prostatic hyperplasia, and lisinopril for hypertension. Which medication could cause a potential drug interaction with lovastatin?

Amiodarone Amiodarone is an inhibitor of CYP3A4, which is extensively involved in the metabolism of lovastatin. When taken together, this combination can increase the level of lovastatin, placing the patient at increased risk for side effects and adverse effects.

Not all statins inhibit

CYP3A4 to the same degree. Pravastatin and fluvastatin inhibit CYP3A4 to a much lesser degree compared with simvastatin and lovastatin, which are the most potent inhibitors

Atorvastatin, lovastatin, and simvastatin are significantly metabolized by

CYP3A4, an isoenzyme of cytochrome P450. Based on this, drug levels of these three statins can be lowered by drugs that induce the CYP3A4 system. This induction increases the rate at which the drugs are metabolized and inactivated. The opposite effect is also observed. Drugs that inhibit the CYP3A4 system will cause a slowing of statin metabolism, resulting in increased drug levels.

Before the administration of a statin, a nurse should assess the following:

Comprehensive health history of the patient to evaluate for conditions that are contraindications to treatment (liver disorder, history of alcohol abuse, pregnancy, breastfeeding) Patient's family history, because some cholesterol disorders are hereditary Patient's risk factors for heart disease Complete list of prescription and over-the-counter drugs the patient is taking Baseline lipid panel, liver function tests, and creatine kinase (CK) level Presence of risk factors for rhabdomyolysis (e.g., advanced age; small body frame; multisystem disease such as chronic kidney disease from diabetes; high dose of statin; low vitamin D or coenzyme Q10 levels; use of gemfibrozil, cyclosporine, or erythromycin; excessive alcohol use; vigorous exercise; hypothyroidism; surgery/trauma)

Additional drug interactions with the HMG-CoA reductase inhibitors include the following:

Concomitant use with warfarin inhibits warfarin metabolism and increases risk for bleeding. Concomitant use with fibrates increases risk for myopathies.

A patient taking atorvastatin is experiencing the adverse effect of myositis. Which manifestations would a nurse expect to see in this patient?

Creatine kinase (CK) elevation Muscle inflammation Muscle pain

Absorption

Depending on the specific statin administered, 5% to 29% of the drug is bioavailable.

Excretion

In general, statins are largely excreted in feces with some statins like atorvastatin undergoing biliary excretion. Ten percent to 20% of the metabolites of lovastatin, pitavastatin, pravastatin, and simvastatin are excreted in the urine. The other statins have minimal to negligible urinary excretion.

A patient who has received a prescription for lovastatin asks the nurse why grapefruit and grapefruit juice should ideally be avoided. Which explanation would the nurse provide?

Increases risk for rhabdomyolysis

Which phrase accurately describes a statin's mechanism of action?

Inhibition of the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase Statins work to decrease cholesterol production through inhibition of the enzyme HMG-CoA reductase.

If a statin therapy is initiated in a patient, the following are some important teaching points to be shared with the patient:

Lipid levels may not be lowered to their maximum extent until 6 to 8 weeks after the start of therapy. Treatment with statin drugs is expected to be a lifelong commitment. Adherence is critical for the lipid parameters to be reduced and remain low. Side effects and adverse effects, especially any muscle aches or pains, darkening of urine, nausea, or vomiting, should be reported to a health care provider. Gastrointestinal distress associated with statins may be reduced by taking the drug with meals or with at least 6 to 8 oz of water (Lilley, 2018). Follow-up is important to assess lipid panel and liver function tests. Exercise and a diet rich in vegetables, fruits, and fiber are important. All health care providers should be notified of the prescription and over-the-counter drugs patients are taking because of the number of potential drug interactions (Lilley, 2018). These drugs may cause fetal harm, and women should avoid pregnancy while taking a statin (Burchum, 2019).

Which statins are significantly metabolized by CYP3A4?

Lovastatin Simvastatin Atorvastatin

Statin drugs are contraindicated in the following:

Patients with a known drug allergy Patients who are pregnant Patients who are breastfeeding Patients with a liver disorder, including those patients with a history of alcohol abuse or with elevated liver enzyme levels

An insurance company is requiring a patient receiving pitavastatin 2 mg to switch to another statin to receive coverage. Which statins and doses are therapeutically equivalent to pitavastatin 2 mg?

Pravastatin 40 mg Simvastatin 20 mg Rosuvastatin 5 mg

Which statements regarding pharmacodynamics and pharmacokinetics of statins are accurate?

Statins reduce cholesterol production through inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase Hepatocytes increase the number of low-density lipoprotein (LDL) receptors in response to decreased cholesterol synthesis by statins to remove cholesterol from circulation.

Which statement regarding the pharmacokinetics of statins is accurate?

Statins undergo first-pass metabolism through the liver, the primary site of statin activity.

Metabolism

Statins undergo first-pass metabolism through the liver, where the majority of the drug is removed from the bloodstream. The liver is the principal site of statin activity. Only a small portion of each dose enters the systemic circulation

Which teaching points would a nurse share with a 33-year-old female patient who was prescribed statin therapy?

The patient should avoid pregnancy while receiving therapy with a statin. Gastrointestinal distress can be minimized by taking with food and/or with at least 6 to 8 oz of water. Ensure she is getting plenty of exercise and a diet rich in vegetables, fruits, and fiber to help lower cholesterol levels.

Potential side effects associated with statins

include musculoskeletal (e.g., muscle cramps and myalgias), dermatological (e.g., rash, pruritus), neurological (e.g., headache), and gastrointestinal (e.g., nausea, constipation, diarrhea, abdominal pain, flatulence, and liver dysfunction) effects (Skidmore-Roth, 2019). Administration of statins with at least 6 to 8 oz of water or a meal can help to alleviate these gastrointestinal side effects

Statins inhibit the

enzyme HMG-CoA reductase, the rate-limiting enzyme that controls cholesterol production in the liver. HMG-CoA reductase is necessary for the liver to make cholesterol, and statins competitively inhibit this enzyme, causing a reduction in cholesterol production. In response to a reduction in cholesterol synthesis, the hepatocytes increase the number of LDL receptors to remove more cholesterol from circulation. In addition, statins reduce apolipoprotein B-100 production, which causes the liver to reduce very low-density lipoprotein (VLDL) production

When statins are concomitantly administered with CYP3A4 substrates requiring the isoenzyme for metabolism, there is an increased risk

for rhabdomyolysis, a condition associated with severe muscle damage. These substrates include macrolide antibiotics, azole antifungals, quinidine, verapamil, amiodarone, grapefruit juice, protease inhibitors, cyclosporine, clarithromycin, diltiazem, and amlodipine. Grapefruit juice causes inactivation of CYP3A4, which leads to increased levels of the statin and also to an increased risk for rhabdomyolysis. There is no consensus on the quantity or volume of grapefruit or grapefruit juice that is safe for patients taking statins to consume. Thus, in general, patients should ideally avoid or at least limit grapefruit juice intake to less than 1 quart daily.

Statins—also known as hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors—are considered first-line drugs in the management of

hyperlipidemia. They are potent drugs for lowering LDL and total cholesterol levels. They also may improve high-density lipoprotein (HDL) cholesterol and triglyceride levels. In addition to their effects on lipid parameters, these drugs have demonstrated improvements in cardiovascular outcomes such as reducing the risk for myocardial infarction, heart failure, and sudden cardiac deat

Which laboratory values will a nurse ensure are ordered for a patient before initiation of a statin?

lipid panel liver enzymes creatine kinase (CK)

to assess the effects of statin therapy what panel must be done

lipid panel should be assessed within 4 to 12 weeks after statin initiation and then every 3 to 12 months as the health care provider determines is necessary. Liver function tests are often assessed to monitor the statin's effect on the liver when the cholesterol parameters are evaluated but may be as frequent as every 3 to 6 months. The patient should also be monitored for the emergence of side effects or adverse effects. CK levels may be assessed in symptomatic patients reporting muscle pains.

Statins may also cause adverse effects. Most notably, statins may cause

myopathies, which are varying degrees of muscle effects. These include generalized muscle pain referred to as myalgias. This may be accompanied by mild increases in CK levels. Myositis refers to muscle pain and inflammation with moderate elevations in CK levels. Rhabdomyolysis is the most severe type of myopathy, in which there is a breakdown of muscle leading to significant elevations in CK levels and the presence of myoglobin in the urine. This can lead to acute renal failure and can be fatal. In addition, elevations in liver function enzymes to three times the upper limit of normal may occur with statin therapy.

Statins differ in potency. Therefore there are

therapeutically equivalent doses that yield the same clinical effects and should be considered when switching patients from one statin to another.

Atorvastatin duration of action

unknown

Atorvastatin onset of action

unknown

simvastatin duration of action

unknown