What are the major drug interactions with Lipitor. How does Lipitor interact with alcohol and food. Which diseases can affect Lipitor’s effectiveness. What precautions should be taken when using Lipitor.

Understanding Lipitor and Its Interactions

Lipitor (atorvastatin) is a widely prescribed medication used to treat high cholesterol and reduce heart-related risks in adults and some children. As with any medication, it’s crucial to be aware of potential interactions that can affect its efficacy or cause adverse effects. This comprehensive guide delves into the various interactions associated with Lipitor, including drug interactions, food and alcohol interactions, and disease interactions.

Drug Interactions with Lipitor: What You Need to Know

Lipitor is known to interact with a significant number of medications. According to the Drugs.com interaction checker, there are 357 drugs that can potentially interact with Lipitor. These interactions are categorized based on their severity:

• 44 major interactions
• 279 moderate interactions
• 34 minor interactions

What constitutes a major drug interaction? Major interactions are highly clinically significant and should be avoided due to the risk outweighing the potential benefits. In contrast, moderate interactions are moderately clinically significant and should usually be avoided unless under special circumstances. Minor interactions are minimally clinically significant but still require attention to minimize risks.

Common Medications That Interact with Lipitor

Some of the most frequently checked interactions with Lipitor include:

• Amlodipine
• Aspirin
• Cymbalta (duloxetine)
• Fish Oil (omega-3 polyunsaturated fatty acids)
• Gabapentin
• Levothyroxine
• Lisinopril
• Metformin
• Omeprazole
• Plavix (clopidogrel)

How can patients manage these interactions? It’s essential to inform your healthcare provider about all medications you’re taking, including over-the-counter drugs and supplements. Your doctor can assess the potential risks and benefits, adjust dosages, or recommend alternative treatments if necessary.

Lipitor and Alcohol: Understanding the Risks

The interaction between Lipitor and alcohol is a common concern for many patients. While moderate alcohol consumption may not significantly impact Lipitor’s effectiveness, excessive alcohol intake can pose risks.

Can alcohol consumption affect Lipitor’s side effects? Yes, both Lipitor and alcohol can potentially cause liver damage. Combining the two may increase this risk. Additionally, excessive alcohol use can raise triglyceride levels, counteracting Lipitor’s cholesterol-lowering effects.

What is considered safe alcohol consumption while taking Lipitor? While it’s best to consult with your healthcare provider, general guidelines suggest limiting alcohol intake to moderate levels. For most adults, this means up to one drink per day for women and up to two drinks per day for men.

Food Interactions with Lipitor: What to Avoid

Certain foods can interact with Lipitor, potentially affecting its absorption or increasing the risk of side effects. Understanding these interactions can help patients optimize their treatment.

Grapefruit and Lipitor: A Potentially Dangerous Combination

One of the most well-known food interactions with Lipitor involves grapefruit and grapefruit juice. Why is grapefruit problematic? Grapefruit contains compounds that can inhibit an enzyme in the intestines responsible for breaking down Lipitor. This can lead to higher levels of the drug in the bloodstream, potentially increasing the risk of side effects.

How much grapefruit is too much? Even small amounts of grapefruit or grapefruit juice can significantly impact Lipitor’s metabolism. It’s generally recommended to avoid grapefruit products entirely while taking Lipitor. If you enjoy grapefruit, discuss alternatives with your healthcare provider.

Other Food Considerations

While grapefruit is the primary food concern, maintaining a healthy diet is crucial when taking Lipitor. A diet high in saturated fats can counteract the medication’s cholesterol-lowering effects. Patients should focus on heart-healthy foods, including fruits, vegetables, whole grains, and lean proteins.

Disease Interactions: When Lipitor May Not Be Suitable

Certain health conditions can affect how Lipitor works in the body or increase the risk of side effects. The Drugs.com interaction checker identifies five disease interactions with Lipitor:

1. Liver disease
2. Rhabdomyolysis
3. Cognitive impairment
4. Diabetes
5. Renal disease

How do these conditions impact Lipitor use? Let’s explore each interaction:

Liver Disease and Lipitor

Lipitor is primarily metabolized by the liver. In patients with liver disease, the drug’s metabolism may be impaired, potentially leading to increased blood levels and a higher risk of side effects. Regular liver function tests are typically recommended for patients taking Lipitor, especially those with a history of liver problems.

Rhabdomyolysis Risk

Rhabdomyolysis is a rare but serious condition characterized by the breakdown of muscle tissue. While all statins carry a risk of rhabdomyolysis, certain factors can increase this risk. These include advanced age, kidney problems, and interactions with other medications.

Cognitive Impairment Concerns

Some studies have suggested a potential link between statin use and cognitive impairment. While the evidence is not conclusive, patients and healthcare providers should be aware of this possible interaction, especially in older adults or those with pre-existing cognitive issues.

Diabetes and Lipitor

Lipitor and other statins have been associated with a slightly increased risk of developing type 2 diabetes. This risk appears to be higher in patients who are already at risk for diabetes. Regular blood sugar monitoring may be recommended for patients taking Lipitor, especially those with prediabetes or other risk factors.

Renal Disease Considerations

Patients with kidney disease may be at increased risk of muscle-related side effects when taking Lipitor. Dosage adjustments may be necessary for patients with severe kidney impairment.

Contraindications: When Lipitor Should Not Be Used

In some cases, the risks of taking Lipitor may outweigh the potential benefits. The medication is contraindicated in certain situations:

• Active liver disease or unexplained persistent elevations in liver enzymes
• Pregnancy
• Breastfeeding

Why is Lipitor contraindicated during pregnancy? Cholesterol is essential for fetal development, and the potential risks to the fetus outweigh the benefits of Lipitor treatment during pregnancy. Women who are pregnant or planning to become pregnant should discuss alternative treatments with their healthcare provider.

Managing Lipitor Interactions: Tips for Patients

Given the numerous potential interactions associated with Lipitor, it’s crucial for patients to take an active role in managing their treatment. Here are some key strategies:

1. Maintain open communication with your healthcare provider
2. Keep an up-to-date list of all medications, supplements, and herbal products you’re taking
3. Report any new symptoms or side effects promptly
4. Follow dosing instructions carefully
5. Attend regular check-ups and complete recommended blood tests
6. Adopt a heart-healthy lifestyle, including a balanced diet and regular exercise

How can patients stay informed about potential interactions? Regularly reviewing medication information, asking questions during healthcare visits, and using reputable drug interaction checkers can help patients stay informed and proactive about their treatment.

The Role of Healthcare Providers in Managing Lipitor Interactions

Healthcare providers play a crucial role in identifying and managing potential interactions with Lipitor. This involves:

• Conducting thorough medication reviews
• Assessing patient-specific risk factors
• Monitoring for side effects and adjusting treatment as needed
• Providing patient education about potential interactions and warning signs
• Collaborating with other healthcare providers to ensure comprehensive care

What should patients expect from their healthcare provider regarding Lipitor interactions? Patients should expect clear communication about potential risks, regular monitoring, and prompt attention to any concerns or side effects they experience.

Understanding and managing Lipitor interactions is crucial for ensuring safe and effective treatment. By staying informed, communicating openly with healthcare providers, and following recommended guidelines, patients can optimize their Lipitor therapy while minimizing potential risks. Remember, every patient is unique, and individualized care is essential when it comes to managing medication interactions.

Lipitor Interactions Checker – Drugs.com

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There are 357 drugs known to interact with
Lipitor (atorvastatin), along with
5 disease interactions, and 2 alcohol/food interactions.

Of the total drug interactions,
44 are major, 279 are moderate, and 34 are minor.

Does Lipitor interact with my other drugs?

Enter other medications to view a detailed report.

• View all 357 medications that may interact with Lipitor
• View Lipitor alcohol/food interactions (2)
• View Lipitor disease interactions (5)

Most frequently checked interactions

View interaction reports for Lipitor (atorvastatin) and the medicines listed below.

• Major
• Moderate
• Minor
• Unknown

• amlodipine
• aspirin
• Aspirin Low Strength (aspirin)
• Cymbalta (duloxetine)
• Fish Oil (omega-3 polyunsaturated fatty acids)
• furosemide
• gabapentin
• hydrochlorothiazide
• Lasix (furosemide)
• levothyroxine
• Lexapro (escitalopram)
• lisinopril
• losartan
• metformin
• metoprolol
• Nexium (esomeprazole)
• Norvasc (amlodipine)
• omeprazole
• Plavix (clopidogrel)
• prednisone
• Protonix (pantoprazole)
• Singulair (montelukast)
• Synthroid (levothyroxine)
• tramadol
• trazodone
• Tylenol (acetaminophen)
• Vitamin B12 (cyanocobalamin)
• Vitamin D3 (cholecalciferol)
• Xanax (alprazolam)
• Zoloft (sertraline)

Lipitor alcohol/food interactions

There are 2 alcohol/food interactions with Lipitor (atorvastatin).

Lipitor disease interactions

There are 5 disease interactions with Lipitor (atorvastatin) which include:

• liver disease
• rhabdomyolysis
• cognitive impairment
• diabetes
• renal disease

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• Side effects
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Related treatment guides

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• High Cholesterol, Familial Homozygous
• Hyperlipoproteinemia
• Hyperlipoproteinemia Type III, Elevated beta-VLDL IDL

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.

Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate	Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor	Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown	No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Alcohol, Other Drugs, Foods, and More

Lipitor (atorvastatin) is a prescription drug that’s used to treat high cholesterol in adults and some children. In addition, Lipitor can be used to reduce other heart-related risks in adults with high cholesterol.

Like other drugs, Lipitor may have interactions.

Some interactions occur because one substance causes another substance to have a different effect than expected. For example, sometimes alcohol, another drug, or a supplement can affect how a drug acts in your body. Interactions can also occur if you have certain health conditions.

Keep reading to learn about Lipitor’s possible interactions, including what you shouldn’t eat or drink while taking Lipitor. And for more information about Lipitor, including details about its uses, see this article.

Certain health conditions or other factors could raise your risk of harm if you take Lipitor. In such cases, your doctor may not prescribe Lipitor for you. These are known as contraindications. The list below includes contraindications of Lipitor.

If you have liver problems. You should not take Lipitor if you have liver problems, including liver disease. Statin drugs such as Lipitor can cause liver problems. If you already have liver problems, taking Lipitor may make your condition worse. Your doctor can recommend a different treatment option for you.

If you’re pregnant. You should not take Lipitor while pregnant. Statin drugs such as Lipitor may cause harm to a fetus if taken during pregnancy. If you’re pregnant or planning a pregnancy, talk with your doctor about other treatment options that are safer for you.

If you’re breastfeeding. It’s not safe to take Lipitor while breastfeeding. It’s not known if Lipitor passes into breast milk or what effects the drug may have on a breastfed child. If you’re currently breastfeeding or planning to breastfeed, talk with your doctor about other treatment options.

If you’ve had an allergic reaction. If you’ve had an allergic reaction to Lipitor or any of its ingredients, your doctor likely won’t prescribe Lipitor. This is because taking the drug could cause another allergic reaction. You can ask them about other treatments that may be better options for you.

Before you start taking Lipitor, talk with your doctor if any of the factors above apply to you. Your doctor can determine whether Lipitor is safe for you to take.

There aren’t any known interactions between Lipitor and alcohol. But your doctor may recommend limiting the amount of alcohol you drink while taking Lipitor. Both Lipitor and alcohol can raise your risk of liver problems, so combining the two may raise your risk of liver problems even more.

If you drink alcohol, talk with your doctor about how much may be safe to consume during your Lipitor treatment.

Before you start taking Lipitor, tell your doctor and pharmacist about any prescription, over-the-counter, or other drugs you take. Sharing this information with them may help prevent possible interactions.

If you have questions about drug interactions that may affect you, talk with your doctor or pharmacist.

The chart below lists drugs that may interact with Lipitor. Keep in mind that this chart does not include all drugs that may interact with Lipitor. For more information about some of these interactions, see the “Drug interactions explained” section below.

Learn more about certain drug interactions that can occur with Lipitor.

Interaction with diltiazem (Cartia XT)

Lipitor may interact with a blood pressure drug called diltiazem (Cartia XT). Diltiazem belongs to a group of drugs called calcium channel blockers.

What could happen

Taking diltiazem with Lipitor can increase your risk of side effects from Lipitor. This is because diltiazem can block your body’s ability to break down Lipitor. This can raise your risk of side effects, including serious side effects such as myopathy (muscle pain), rhabdomyolysis (muscle breakdown), and liver problems.

What you can do

If you already take diltiazem, tell your doctor before starting your Lipitor treatment. Your doctor may recommend monitoring you more closely for symptoms of myopathy, rhabdomyolysis, and liver problems during your treatment. In some cases, they may prescribe a lower dose of Lipitor for you.

If you have questions about taking Lipitor with diltiazem, talk with your doctor.

Interaction with certain antifungal drugs

Lipitor can interact with a certain type of antifungal drug called azole antifungals.

Examples of azole antifungal medications include:

• itraconazole (Sporanox)
• fluconazole (Diflucan)
• ketoconazole

What could happen

Taking Lipitor with certain antifungal medications may raise your risk of side effects from Lipitor. Azole antifungals can decrease your body’s ability to break down Lipitor. This can cause Lipitor to build up in your body, which can raise your risk of side effects. In some cases, side effects may be serious, such as myopathy, rhabdomyolysis, and liver problems.

What you can do

If you need to take an antifungal drug during your Lipitor treatment, talk with your doctor first. In some cases, they may be able to recommend specific antifungal treatments that don’t interact with Lipitor.

If you need to take an azole antifungal with Lipitor, your doctor may monitor you more closely for symptoms of side effects such as myopathy, rhabdomyolysis, and liver problems. Or your doctor may lower your Lipitor dose.

Interaction with birth control pills

Lipitor may interact with certain birth control pills. Examples include:

• desogestrel/ethinyl estradiol (Enskyce, Kariva)
• drospirenone/ethinyl estradiol (Loryna, Yaz)
• ethinyl estradiol/norethindrone (Junel, Balziva)

What could happen

Taking birth control pills with Lipitor may raise your risk of side effects from your birth control pills. This is because Lipitor can increase birth control hormone levels in your blood. This may raise your risk of side effects from your birth control pills.

What you can do

If you want to take Lipitor with birth control pills, talk with your doctor first. They may monitor you more closely for side effects from your birth control pills.

If you do experience more side effects than usual, your doctor may recommend a different birth control option for you. For example, a vaginal ring such as etonogestrel ethinyl estradiol (NuvaRing) or a contraceptive injection such as medroxyprogesterone (Depo-Provera) may be better options.

If you have questions about using Lipitor with birth control pills, talk with your doctor.

Lipitor may have other interactions. They could occur with foods, supplements, vaccines, or even lab tests. See below for details. Note that the information below does not include all other possible interactions with Lipitor.

Does Lipitor interact with food?

You should avoid grapefruit and grapefruit juice during your Lipitor treatment. Grapefruit and grapefruit juice can block your body’s ability to break down Lipitor. This can cause a buildup of Lipitor in your body, which raises your risk of side effects. In some cases, these side effects may be serious, such as myopathy (muscle pain), rhabdomyolysis (muscle breakdown), and liver problems.

Does Lipitor interact with supplements?

Before you start taking Lipitor, talk with your doctor and pharmacist about any supplements, herbs, and vitamins you take. Sharing this information with them may help you avoid possible interactions.

Your doctor may recommend avoiding red yeast rice when you’re taking Lipitor. Red yeast rice and Lipitor work in similar ways to lower cholesterol levels. So taking the two together may increase your risk of side effects such as myopathy, rhabdomyolysis, and liver problems.

Be sure to talk with your doctor about any supplements you take along with Lipitor. They can determine if they may be safe to take during your Lipitor treatment.

If you have questions about interactions that may affect you, talk with your doctor or pharmacist.

Lipitor interactions with herbs

Lipitor can interact with St. John’s wort. This herbal supplement can be used to treat depression.

St. John’s wort can cause your body to break down Lipitor too quickly, which can make Lipitor less effective. If you take St. John’s wort, your doctor may recommend that you stop taking it during your Lipitor treatment.

Lipitor and vitamins

There are currently no reports of Lipitor interacting with vitamins. But this doesn’t mean that vitamin interactions won’t be recognized in the future.

For this reason, it’s still important to check with your doctor or pharmacist before taking any of these products while taking Lipitor.

Does Lipitor interact with vaccines?

No, Lipitor isn’t known to interact with any vaccines. If you have questions about getting specific vaccines during your Lipitor treatment, talk with your doctor or pharmacist.

Does Lipitor interact with lab tests?

No, Lipitor isn’t known to interact with lab tests. But if you need to have lab tests, make sure the healthcare professional giving you the test knows about all medications you currently take. They can make sure there won’t be any interactions between your lab tests and medications.

Does Lipitor interact with cannabis or CBD?

Cannabis (commonly called marijuana) and cannabis products, such as cannabidiol (CBD), have been specifically reported to interact with Lipitor. It’s possible for cannabis to either increase or decrease the amount of Lipitor in your blood. This may increase your risk of side effects, including myopathy (muscle pain), rhabdomyolysis (muscle breakdown), and liver problems. Sometimes, this interaction can cause Lipitor to be less effective.

Before you start treatment with Lipitor, tell your doctor and pharmacist if you use cannabis. By sharing this information with them, you may help prevent possible interactions.

Note: Cannabis is illegal at a federal level but is legal in many states to varying degrees.

Certain medical conditions or other health factors may raise the risk of interactions with Lipitor. Before taking Lipitor, talk with your doctor about your health history. They’ll determine whether Lipitor is right for you.

Health conditions or other factors that might interact with Lipitor include:

Liver problems. If you have any liver problems, tell your doctor before taking Lipitor. This drug may cause liver problems. And if you already have a liver condition, taking Lipitor may make it worse. Due to this risk, if you have liver problems, your doctor will likely recommend that you take a different medication for your cholesterol.

Kidney problems. Before starting treatment with Lipitor, tell your doctor about any kidney problems you have. Lipitor can cause serious side effects, such as myopathy or rhabdomyolysis. If you have kidney problems, you may have a higher risk of these side effects from Lipitor. If you have kidney problems and take Lipitor, your doctor may monitor you more closely for side effects during your treatment.

Diabetes. In rare cases, Lipitor can raise your risk of high blood sugar. If you have diabetes, taking Lipitor can make your condition worse. Your doctor may recommend monitoring your blood sugar levels more often during your Lipitor treatment.

Stroke. Before taking Lipitor, tell your doctor if you’ve had a stroke. In rare cases, Lipitor can increase your risk of having a stroke. If you’ve recently had a stroke, your risk of having another stroke may be higher during your Lipitor treatment. Your doctor can determine if Lipitor may be safe for you.

Underactive thyroid. If you have an underactive thyroid, you may have a higher risk of myopathy and rhabdomyolysis while taking Lipitor. If you have an underactive thyroid, talk with your doctor before taking Lipitor. They may monitor you more closely during your treatment, or they may prescribe treatment for your thyroid condition.

Pregnancy. Lipitor should not be used during pregnancy. Taking this drug while pregnant could raise the risk of problems with fetal development (commonly called birth defects). Due to these possible risks, your doctor will likely recommend a different treatment if you’re pregnant or planning a pregnancy.

Breastfeeding. It’s not safe to take Lipitor while breastfeeding. At this time, it’s not known if the drug passes into breast milk or what effects it may have on a breastfed child. If you’re breastfeeding or planning to breastfeed, talk with your doctor about your treatment options.

Allergic reaction. If you’ve had an allergic reaction to Lipitor or any of its ingredients, your doctor will likely not prescribe Lipitor. This is because taking the drug could cause another allergic reaction. You can ask them about other treatments that may be better choices for you.

Find answers to some frequently asked questions about Lipitor and possible interactions.

Is it safe to take Lipitor with nonsteroidal anti-inflammatory drugs (NSAIDs)?

Yes, it’s likely safe to take Lipitor along with NSAIDs. There aren’t any known interactions between these drugs. NSAIDs are used to treat pain, swelling, or fever. Examples of NSAIDs include:

• aspirin
• ibuprofen (Advil)
• naproxen (Aleve)

If you have questions about taking NSAIDs with Lipitor, talk with your doctor or pharmacist.

Can Lipitor be taken along with ezetimibe (Zetia) to treat my high cholesterol?

Yes, it’s likely safe to take ezetimibe (Zetia) with Lipitor. There aren’t any known interactions between the two drugs.

Both Lipitor and Zetia are approved to treat high cholesterol. And in some cases, taking Zetia with statin drugs such as Lipitor is recommended to treat high cholesterol.

Before you start treatment for high cholesterol, your doctor will recommend the best plan for you. In some cases, they may recommend taking Zetia and Lipitor together.

Are there interactions between Lipitor and caffeine?

It’s likely safe for you to have caffeine along with Lipitor. There aren’t any known interactions between Lipitor and caffeine. Caffeine is present in certain food and drinks, such as coffee, chocolate, and tea.

If you’d like to have caffeine while you’re taking Lipitor, talk with your doctor. They can determine how much caffeine may be safe during your treatment.

Does Lipitor interact with lisinopril (Zestril)?

No, there aren’t any known interactions between Lipitor and lisinopril (Zestril). It’s likely safe for you to take these medications together.

Lisinopril is used to lower blood pressure in people with high blood pressure. In some cases, your doctor may recommend taking Lipitor with lisinopril.

Does Lipitor interact with the nutrient CoQ10?

No, there aren’t any known interactions between Lipitor and the nutrient CoQ10. This is an antioxidant that’s found in your body. It helps improve energy and protects your body from damage.

Statin drugs such as Lipitor may actually decrease the amount of CoQ10 in your body. This can increase your risk of certain side effects from Lipitor, such as myopathy (muscle pain) and rhabdomyolysis (muscle breakdown).

Taking CoQ10 supplements along with Lipitor may lower your risk of these side effects. Talk with your doctor to see if they may recommend taking CoQ10 supplements along with Lipitor.

Is it safe for me to take Lipitor with sildenafil (Viagra)?

Yes, it’s likely safe to take Lipitor and sildenafil (Viagra) together. There aren’t any known interactions between these drugs. Viagra is used to treat erectile dysfunction.

But before you start taking Viagra, be sure to tell your doctor about any other drugs you take. This can help prevent interactions between Viagra and your other medications.

Taking certain steps can help you avoid interactions with Lipitor. Before starting treatment, talk with your doctor and pharmacist. Things to discuss with them include:

• Whether you drink alcohol or use cannabis.
• Other medications you take, as well as any vitamins, supplements, and herbs. Your doctor or pharmacist can help you fill out a medication list.
• What to do if you start taking a new drug during your Lipitor treatment.

It’s also important to read Lipitor’s label and other paperwork that may come with the drug. You may see colored stickers on the label that describe interactions. And the paperwork (sometimes called the patient package insert or medication guide) may have other details about interactions. (If you did not get paperwork with Lipitor, ask your pharmacist to print a copy for you.) If you need help understanding this information, your doctor or pharmacist can help.

Taking Lipitor exactly as prescribed can also help prevent interactions.

If you still have questions about Lipitor and its possible interactions, talk with your doctor.

Questions you may want to ask them include:

• Do other drugs that treat my condition also have similar interactions?
• Should I let you know if I start taking other medications or supplements during my Lipitor treatment?
• Does my risk of interactions depend on my Lipitor dosage?
• Would spacing out my medications lower my risk of interactions?

To learn more about Lipitor, see these articles:

• All About Lipitor
• Side Effects of Lipitor: What You Need to Know
• Dosage for Lipitor: What You Need to Know

To get information on different conditions and tips for improving your health, subscribe to any of Healthline’s newsletters. You may also want to check out the online communities at Bezzy. It’s a place where people with certain conditions can find support and connect with others.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Drug interactions: are there “ideal” drugs for use in polypharmacy? | Ostroumova O.

D., Batutina A.M., Zykova A.A.

А Arterial hypertension (AH) is considered to be one of the most frequent risk factors for death in the world. The prevalence of hypertension progressively increases with age. In of the Russian Federation in persons of older age groups, the frequency of AH exceeds 80% . Only 16% of them receive treatment, and the level of blood pressure (BP) is under control in only 8%. One of the main aspects of the recommendations of the VNOK (2001) is the desire to control the level of blood pressure at numbers less than 140/90 mmHg in most patients (including the elderly) and less than 130/85 mm Hg. in patients with diabetes mellitus. Level less than 125/75 mmHg. should be achieved in patients with impaired renal function and proteinuria more than 1 g / day. Since the administration of a single antihypertensive drug reduces blood pressure by an average of 10/5 mmHg, the administration of several drugs with different mechanisms of action is often required to achieve the target blood pressure level. The use of several drugs in medium doses is often more effective and safe than increasing the dose of one drug to the maximum. This positive aspect of using drug combinations to achieve better disease control is well known. The combination of antihypertensive drugs is also used to prevent the occurrence of toxic effects. For example, type 1 angiotensin II receptor antagonists (ARAs) can cause an increase in plasma potassium levels, and thiazide diuretics can decrease it. Therefore, the combination of ARA + thiazide diuretic is one of the most optimal .

However, be aware that drug interactions can lead to very serious adverse effects. According to available data, about 50% of adverse reactions to drugs develop as a result of drug interactions, and among patients who died as a result of adverse drug reactions, approximately 30% died as a result of drug interactions.

Therefore, combinations of drugs with the least degree of interaction are the most promising – in order to reduce the formation of adverse effects, reduce the effectiveness of one of them and / or both.

Consideration should also be given to the relationship between age and susceptibility to drug interactions. Since elderly patients are more likely to be prescribed different drugs, the potential for drug interactions in this population is quite high. For example, studies in elderly patients have shown that dihydropyridines cause a more pronounced decrease in blood pressure in them compared to young people, which is associated with their reduced ability to compensatory reactions. Thus, for many drugs there is a problem of individual dose selection for elderly patients. In conditions of taking several drugs in patients of this group, it seems appropriate to choose a drug with a more favorable pharmacokinetic profile. So, ARA – eprosartan ( Teveten ) is more actively absorbed in elderly patients, which is expressed in doubling the maximum concentration in blood serum and reducing the time to reach them. However, in the course of clinical studies, no changes in tolerability and efficacy of the drug were observed, which avoids the need for individual dose selection.

Another feature of this age group is a decrease in autonomic reactions due to a decrease in the sensitivity of baroreceptors, which leads to an increased risk of hypotension in response to the introduction of an average therapeutic dose of the drug. For the group of angiotensin II receptor antagonists, the degree of such risk is determined by the reversibility of binding to arterial angiotensin II receptors. So, valsartan, irbesartan, candesartan and the active metabolite of losartan are characterized by non-competitive kinetics, and their binding to receptors is irreversible, while for eprosartan (Teveten) the blockade is dose-dependent, which indicates a competitive connection with arterial receptors. This reversible binding means that if the body produces an increased amount of angiotensin II (in response to a drop in blood pressure), then eprosartan (Teveten) can be displaced from its binding sites.

Based on this, the importance of assessing possible drug interactions in the selection of therapy at the present stage of development of pharmacology becomes obvious. It is necessary to take into account the constant increase in the number of patients over 65 years of age who require the simultaneous administration of several drugs, which leads to an increase in the percentage of adverse drug interactions. Unfortunately, at the moment there are no adequate measures to monitor this process. Polypharmacy occurs in 56% of patients under 65 years of age and in 73% of patients over 65 years of age . Taking two drugs leads to drug interactions in 6% of patients. Taking 5 drugs increases their frequency by up to 50%. When taking 10 drugs, the risk of drug interactions reaches 100% . One study showed that the average number of drugs taken by patients (both doctor-prescribed and self-administered) was 10.5, and in 96% of cases, doctors did not know exactly what their patients were taking.

Thus, the problem of the interaction of drugs in modern conditions is one of the most urgent problems of practical medicine. Knowledge of the main drug interactions will allow the doctor to increase the safety of the therapy.

Under the interaction of drugs (drugs) understand the change in the action of one drug under the influence of another . More often this leads to adverse reactions, but sometimes it can be clinically beneficial. A drug that causes an interaction is called a provocative or inductor drug, and a drug whose action changes is called the object of interaction. Although sometimes the interaction of drugs may change the effects of both drugs.

Drugs that tend to cause interactions . These include, for example, drugs that actively bind to proteins and displace the drug-object from the complex with these proteins (acetylsalicylic acid, sulfonamides, etc.).

Drugs that may be the object of interaction . They are more often drugs that have a high dependence of the effect on the dose and even a slight change in dose is accompanied by a significant change in the therapeutic effect. Drugs with a low toxic-to-therapeutic ratio (i. e., those drugs for which a very small increase in therapeutic dose results in a toxic effect) are also susceptible to interactions that increase their toxicity as a target drug. All this applies, in particular, to anticoagulants, antihypertensive drugs, cardiac glycosides and a number of other drugs.

There are several types of drug interactions – pharmaceutical, pharmacokinetic and pharmacodynamic. Pharmaceutical interactions are physicochemical interactions of a drug with a solution for intravenous infusion or two drugs in one solution. Such interactions lead to the loss of activity of the drug-object. To avoid this, if possible, it is necessary to administer intravenous drugs one at a time. Pharmacokinetic interactions occur when the absorption (absorption), distribution or excretion (metabolism or excretion) of a target drug is altered by another drug that induces the interaction.

The greatest clinical significance is the interaction during drug metabolism (most often in the liver). Such an interaction is observed if the metabolism of the target drug is inhibited or accelerated by another drug (the “provocative” drug). The basis of metabolic processes is oxidation, dependent on the presence of NADPH + and heme-containing protein – cytochrome P450 . In total, more than 50 human CYPs have been identified, of which only a few (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4) are responsible for the metabolism of most drugs.

CYP3A4 is one of the most important, because it transforms, at least partially, about 60% of oxidizable drugs. Although CYP3A4 activity varies widely, it is not subject to genetic polymorphism. The location of CYP3A4 on small intestinal apical enterocytes and hepatocytes facilitates its important role in drug metabolism prior to entry into the systemic circulation, known as first pass metabolism. CYP3A4 plays an important role in the metabolism of lovastatin, simvastatin, and atorvastatin. Since lovastatin and simvastatin have initially very low oral bioavailability (5%), these drugs show a significant (10-20-fold) increase in plasma concentration when amiodarone, diltiazem, erythromycin and some other drugs (i. e. CYP3A4 inhibitors) are used together. ). Atorvastatin has a higher bioavailability and its concentration when using CYP3A4 inhibitors increases by 2-4 times. In contrast to these drugs, pravastatin is only slightly metabolized by CYP3A4, while fluvastatin is metabolized by CYP2C9.and may be considered as an alternative in patients receiving CYP3A4 inhibitors.

Other cytochrome CYP2D6 is involved in the metabolism of 15 to 20% of drugs. Expressed mainly in the liver. Unlike CYP3A4, its activity is not as affected. However, there are significant individual differences in its activity. Most of the variations are due to genetic polymorphism, as a result of mutations, CYP2D6 exists in several different forms (alleles). Metabolism via CYP2D6 is the main elimination route for many antiarrhythmic drugs, b-blockers, tricyclic antidepressants, and other drugs. For example, metoprolol and timolol are inactivated by CYP2D6. When administered, for example, with amiodarone (an inhibitor of CYP2D6), there is an increased risk of significant bradycardia (heart rate less than 40 per minute) and severe drowsiness at usual clinical doses. This is true even when timolol eye drops are prescribed for the treatment of glaucoma. Atenolol is a b-blocker that is not metabolized. It is excreted unchanged from the body and can be used when the administration of metoprolol and timolol leads to drug interactions.

The CYP2C family of cytochromes in humans is mainly represented by four enzymes involved in drug metabolism, of which CYP2C9 plays the most important role in drug metabolism and makes up at least 20% of hepatic cytochrome proteins. While this family of cytochromes is responsible for the metabolism of fewer drugs than CYP3A4 and CYP2D6 discussed above, CYP2C9 is of particular importance as it metabolizes warfarin. Warfarin is an oral anticoagulant that is increasingly being used to prevent thromboembolism. While the average daily dose is about 5 mg, the need for warfarin is very variable and ranges from 0.5 to 60 mg. Since warfarin has a narrow therapeutic index (a slight increase in plasma concentration can lead to a significant increase in the effect of the drug), a decrease in the anticoagulant effect with the use of inducers (ethanol, phenobarbital, etc. ) or an increase with the use of CYP2C9 inhibitors(particularly amiodarone, statins) is a common cause of adverse side effects during long-term warfarin therapy.

Another type of pharmacokinetic interaction is interaction at the transport level . More and more attention is paid to the role of transport proteins in the distribution and achievement of the clinical effect of drugs. The properties of P-glycoprotein, which transports many structurally different drugs, are best studied. It is located on the surface of the epithelial cells of the small intestine, the membrane of the bile ducts of the liver, the proximal tubules of the kidneys and epithelial cells that are part of the blood-brain and blood-testicular barriers. P-glycoprotein influences the distribution of drugs by limiting their absorption in the intestine, facilitating their excretion by bile and urine secretion, and reducing their penetration into the brain and testicles.

Thus, digoxin in the human body is not metabolized and is excreted unchanged through the kidneys and bile. Several clinical studies have shown that with the simultaneous administration of P-glycoprotein inhibitors (verapamil, amiodarone), plasma concentrations of digoxin increased by 50-300%. This may occur as a result of inhibition of digoxin excretion via the intestines, kidneys or liver and often leads to symptoms of glycoside intoxication.

At pharmacodynamic interactions “provocative” drug changes the effect of the target drug at the point of its application.

Direct pharmacodynamic interactions. Direct pharmacodynamic interactions occur when two drugs act either at the same site (antagonism or synergy) or at two different sites, but with the same end result.

1. Antagonism at the same site of application. There are many examples of such interaction. Some of these are clinically beneficial, such as the elimination of the effects of warfarin by vikasol.

2. Synergism at the same application site. For example, verapamil and b-blockers, when used together, are more likely to cause the development of conduction disturbances than when they are used alone. This interaction takes place in the specialized tissue of the conduction system of the heart. Their combination also increases the risk of heart failure, since both of them cause a negative inotropic effect on the heart muscle.

3. Synergy of similar actions in different places of application. Any drug that has a CNS depressant effect can potentiate the action of another drug with a similar effect, whether both drugs act on the same receptor or on different receptors. The most typical example is the interaction of different groups of antihypertensive drugs.

Indirect pharmacodynamic interactions . In an indirect pharmacodynamic interaction, the pharmacological, therapeutic, or toxic effects of the “provocative” drug alter the therapeutic or toxic effect of the target drug. However, these two effects are not related to each other and do not influence each other. Thus, a change in water or electrolyte balance can secondarily affect the action of some drugs. The action of cardiac glycosides is enhanced with hypokalemia, while the effect of some antiarrhythmic drugs (lidocaine, quinidine, novocainamide) is reduced.

However, there are also drugs that do not enter into metabolic or transport interactions, which dramatically increases their safety in case it is necessary to prescribe several medications for the treatment of a patient.

Thus, ARA II are eliminated in various ways. Losartan is eliminated by metabolism by CYP3A4 or CYP2C9, candesartan and irbesartan by CYP2C9, and telmisartan is secreted in the bile via P-glycoprotein, while eprosartan (Teveten) and valsartan are not metabolized. It should be noted that eprosartan (Teveten) undergoes only minor biotransformation. Only about 2% of the administered dose of the drug is transformed into a conjugate with glucuronic acid, and the rest is excreted unchanged in the feces and urine without significant cumulation. Eprosartan (Teveten) does not change or inhibit the activity of cytochrome P450 isoenzymes, and for this reason it does not interact with other drugs .

Therefore, changes in the clinical effect of a drug as a result of drug interactions are often due to a disruption in the activity of the mechanism(s) responsible for drug elimination. This includes, in particular, the induction and inhibition of the processes responsible for the metabolism of the drug with the help of liver cytochromes P450 and / or drug transport (P-glycoprotein).

Thus, in modern conditions, when patients receive several drugs at the same time to treat their disease (diseases), the problem of drug interaction seems to be extremely important for a practical doctor. After all, adverse events that have arisen as a result of drug interactions can lead to a loss of therapeutic effect or increased toxicity (overdose). It is extremely important for the practitioner to have an understanding of the main mechanisms of drug interactions, since in many cases potential interactions can be predicted based on knowledge of the drug (oral bioavailability, elimination mechanism, severity of toxic effects).