Deciphering Prescription Drugs’ Package Inserts for Safe and Effective Medication Use: Insights from a Toxicologist

Lots of adults take prescription drugs, and the usage rates are continuously increasing. Of approximately 1.3 million emergency room visits in the US, caused by side effects that occur annually, patient education is becoming increasingly important.

All prescription drugs come with instructions on how to use them safely and effectively. That may be depending on the medication multiple types of information included: patient information leaflet, medication manual and instructions for use. One or more of these documents can be folded into the box or included as a printed page by your pharmacist.

I am a scientist which studies how drugs and other chemicals affect human health. Although they may look intimidating, package inserts – and especially the prescribing information – can help patients better understand the science in the pill bottle and blister pack, among other things.

What can I learn from package inserts?

An often overlooked part of the package insert is the prescribing information. Although written primarily for healthcare professionals, it contains a wealth of information about how the medication interacts with the body.

If the prescribing information is not included with your prescription, you can often find a copy at the National Institutes of Health’s DailyMed website or other drug information websites.

As an example, let’s look at one of the most prescribed drugs in the US, atorvastatin (Lipitor). Among other effects, it lowers elevated levels of cholesterol in general, as well as levels of low-density lipoprotein cholesterol – LDL, or “bad” cholesterol.

Reading the package insert can answer some important questions about the drug. If you would like to participate, a copy of the prescription information for Lipitor can be found here.

How does the drug work?

To answer this question, please refer to the “Mechanism of action” and “Pharmacodynamics” subsections of the Package Leaflet.

Mechanism of action and pharmacodynamics are related concepts. The mechanism of action describes the chemical and molecular interactions that cause a drug’s therapeutic or toxic effects. Pharmacodynamics refers to “what the drug does to the body,” including its mechanism of action and how other factors such as drug concentration affect its effects.

Often a drug’s mechanism of action is related to its interaction with cell receptors and enzymes involved in mediating specific signals and biochemical reactions in the body.

In the case of Lipitor, the prescribing information tells us three important things about how the drug works. First, the liver is the primary site that produces cholesterol in the body and the area that the drug should target. Second, the drug works by inhibiting an enzyme involved in cholesterol production HMG-CoA reductase. And third, the drug increases the number of LDL cholesterol receptors on cell surfaces, ultimately increasing the number of LDL cholesterol receptors catabolismor metabolic breakdown of LDL cholesterol.

Where does the drug go in my body?

Before answering this question, let’s start with some background information in the ‘Pharmacokinetics’ subsection.

Pharmacokinetics can be thought of as “what the body does with the drug”. It focuses on four major processes the body undergoes in response to the chemical: absorption, or how the drug gets into the body; distribution, or how the drug is distributed throughout the body; metabolism, or how the drug is converted to other chemical forms; and excretion, or how the drug is eliminated from the body.

The pharmacokinetics of a drug are determined by factors related to the chemical itself and the person taking the drug. For example, disease state, age, sex, and genetic makeup can all cause the same medication to work differently in different people.

Now let’s look at the “Distribution” subsection.

For Lipitor, the package insert does not specifically say where the drug enters the body, but it does point out that the volume of distribution amounts to 381 liters. The volume of distribution is the ratio of the total amount of the drug in the body to its concentration in the blood. A reading greater than about 30 liters suggests it has the drug body tissues are invaded and is not limited to the bloodstream. For reference, the drug warfarin, which prevents blood clots, is tightly bound to proteins in the blood and has a volume of distribution of only 8 liters. On the other hand, chloroquinean antimalarial drug that penetrates body fat has a value of 15,000 liters.

Is the drug causing the effects or its by-products?

While the therapeutic effects of most drugs come from the chemical compound they are made of, many of them break down active metabolites in the body that also have some relevant biological effects.

Some medications are administered in one inactive form called a prodrug which the body converts into metabolites with the desired therapeutic effects. Drug manufacturers generally use prodrugs because they have better pharmacokinetics – such as better absorption and distribution in the body – than the active form of the drug.

In the case of Lipitor, the “Metabolism” subsection under “Pharmacokinetics” tells us that the drug is broken down into several products and that these metabolites contribute significantly to its therapeutic effect.

How long will the drug stay in my system?

An important property of a drug to consider in this case is the half-life, which is the time it takes for the concentration of the drug to drop to half of its original amount in the body. Information on a drug’s half-life can be found in the ‘Excretion’ subsection under ‘Pharmacokinetics’.

The half-life of Lipitor is approximately 14 hours. If you were to stop taking the medication, 97% of the drug would be gone from your blood after about three days or five half-lives.

The package insert provides another interesting piece of information: Because Lipitor’s active metabolites have a longer half-life than the drug itself, the half-life for its cholesterol-enzyme-inhibiting effects is 20 to 30 hours. This means that the effects of the drug can persist even after the drug itself is out of your system.

Why do I have to take medicines with food or at certain times?

Eating food can change the amount and rate at which a drug is absorbed into the body in several ways, including changing the acidity of the digestive system, altering the release of bile, and increasing blood flow to the intestines.

Specifically for Lipitor, the answer to this question can be found in the “Absorption” subsection under “Pharmacokinetics”. Food decreases the rate and extent of Lipitor absorption, but does not significantly affect the reduction of LDL cholesterol.

Interestingly, the package insert also states that the blood concentration of the drug is significantly lower in the evening than in the morning, but the reduction in LDL cholesterol levels is the same regardless of when the drug is taken.

The result of all this is on the drug label on the outside of the package: Lipitor can be taken with or without food. Morning or evening is not specified, but the recommendation is to take it at the same time every day.

Why is my doctor asking about other medications I’m taking?

Drugs can interact in ways that affect their safety and effectiveness. For example, two drugs may rely on the same enzyme system in the body to break them down. Taking them at the same time could eventually lead to higher than expected levels of one or both drugs in the body.

Information to answer this question can be found in the “Drug Interactions” section.

One of the drug classes of concern to Lipitor is “strong inhibitors of CYP 3A4,” an enzyme that plays a key role in metabolizing many drugs. Because Lipitor itself is broken down by this enzyme, taking it with drugs that inhibit CYP 3A4, such as the antibiotic clarithromycin or the antifungal drug itraconazole, can lead to an increased concentration in the blood and possible side effects.