What are the Amlodipine Interactions with Other Medications?

Summary

Amlodipine interactions primarily occur at the level of liver enzymes. CYP 450, a wide family of enzymes (proteins that transform molecules), is the main site of amlodipine metabolism (transformation to an easy-to-eliminate substance).

For this reason, amlodipine interactions are produced when amlodipine is given with other drugs that are metabolized by this same group of enzymes, including ritonavir, phenytoin, and carbamazepine, among others. Find more amlodipine interactions to bear in mind in this article.

Contents show

Summary
Introduction
1. CYP3A4 Inhibitors Increase Amlodipine Effect
Ritonavir
Diltiazem
Food and Drug Administration CYP3A4 Inhibitors Drugs List
2. CYP3A4 Inducers Decrease Amlodipine Effect
FDA CYP3A4 Inducers Drugs List
3. Impact of Amlodipine on Other Drugs
Simvastatin
Cyclosporine and Tacrolimus
Lofexidine
Conclusion

Introduction

Amlodipine, a calcium channel blocker, is a medication that relaxes the blood vessels and is used to reduce high blood pressure or to treat chest pain (angina). Alone or in combination with other drugs, it is also used to treat impaired blood flow through coronary arteries (blood vessels that supply blood to the heart muscle), most commonly due to cholesterol deposits on their walls (coronary artery disease). (1-3)

For over 30 years of clinical use, interactions between amlodipine and some medications have been identified. Some drugs, like ritonavir, ketoconazole, erythromycin, and dantrolene, may increase the effect of amlodipine, while others, such as carbamazepine, may reduce the amlodipine levels in the blood and by that its clinical effect. (4)

This article explains the effects that certain medications have on amlodipine, but also the effects that amlodipine has on some drugs. Keep reading to find out what medications interact with amlodipine and the recommendations in such cases.

1. CYP3A4 Inhibitors Increase Amlodipine Effect

Medications that inhibit the activity of the CYP3A4 enzyme can increase amlodipine levels in the body and its antihypertensive effect.

CYP3A enzymes in the human body are responsible for drug metabolism. These can be found in the liver and the gastrointestinal tract. Four major enzymes belong to this CYP3A group: CYP3A3, CYP3A4, CYP3A5, and CYP3A7. CYP3A4 enzyme is the one that metabolizes up to 50% of the drugs and is involved in drug interactions. (5-6)

The metabolism of amlodipine is held in the liver, where the active substance is transformed into inactive metabolites. (7) So, any impact on the liver enzymes’ activity may affect the therapeutic effect of amlodipine.

Some medications may inhibit the activity of CYP3A enzymes, and consequently, the available amount of amlodipine in the body increases. As a result of this drug-drug interaction, and due to the increased amount of amlodipine and its effect, hypotension may occur. (3)

Ritonavir

Ritonavir is a well-known CYP3A4 inhibitor. This medication is used to treat HIV and hepatitis C virus infections. Ritonavir is used alone or in combination with danoprevir, elvitegravir, indinavir, lopinavir, etc. Therefore, the drug combination that includes ritonavir can inhibit enzyme activity and increase amlodipine’s serum concentration. (8)

Diltiazem

Co-administration with diltiazem, although infrequently administered together, is another example of drug-drug interaction. Diltiazem increases the Area under the curve (AUC) of amlodipine by 60%, which means increased amlodipine concentration in the blood plasma. This interaction may result in a slow heart rate (bradycardia), heartbeat pause or stop (sinus arrest), or the heart might not pump sufficient blood volume as the body needs (decreased cardiac output). Call your doctor and tell them if this happens to you. (9)

Food and Drug Administration CYP3A4 Inhibitors Drugs List

Below you may find some CYP3A4 strong inhibitors listed by the Food and Drug Administration (FDA):

Adagrasib,
Atazanavir,
Ceritinib,
Clarithromycin,
Cobicistat,
Darunavir,
Idelalisib,
Indinavir,
Itraconazole,
Ketoconazole (Systemic),
Levoketoconazole,
Lonafarnib,
Lopinavir,
Mifepristone,
Nefazodone,
Nelfinavir,
Nirmatrelvir and Ritonavir,
Ombitasvir,
Paritaprevir and Ritonavir,
Ombitasvir,
Paritaprevir,
Ritonavir and Dasabuvir,
Posaconazole,
Ritonavir,
Saquinavir,
Telithromycin,
Tucatinib, and
Voriconazole. (8, 10)

FDA has categorized the following commonly used medications as moderate or weak CYP3A4 inhibitors:

Abiraterone,
Aprepitant,
Berotralstat,
Clindamycin,
Clozapine,
Conivaptan,
Crizotinib,
Cyclosporine,
Desvenlafaxine,
Diltiazem,
Dronedarone,
Duvelisib,
Erythromycin (Systemic),
Fedratinib,
Fluconazole,
Fluvoxamine,
Fosamprenavir,
Fosnetupitant,
Grapefruit Juice,
Haloperidol,
Imatinib,
Indalpine,
Isavuconazole,
Isavuconazonium Sulfate,
Lefamulin,
Lenacapavir,
Letermovir,
Luliconazol,
Miconazole,
Milnacipran,
Netupitant,
Nicardipine,
Nilotinib,
Primaquine,
Ribociclib,
Schisandra,
Simeprivir,
Tepotinib,
Tioconazole,
Verapamil, and
Zimelidine (8, 11)

In addition to hypotension, some side effects, such as edema, may occur due to the co-administration of CYP3A4 inhibitor and amlodipine. (3)

Aside from drugs, some food can inhibit CYP3A4 activity too. For example, grapefruit juice is a well-known CYP3A4 inhibitor. Its inhibitors’ effect depends on the products’ concentration, dose, and preparation. (8)

In case of interaction or side effects appearance, the doctor might reduce the daily dose of amlodipine. (3)

2. CYP3A4 Inducers Decrease Amlodipine Effect

Another group of medications has the opposite effect on CYP3A4 enzymes; they induce the enzymes’ activity. These medications are called CYP3A4 inducers. If the drug supports the enzyme’s activity, it will increase the metabolism of amlodipine, leading to faster clearance. (3)

Yet, no data is available on how much active amlodipine amount is affected. However, it may result in less control of blood pressure. This is why the doctor might closely monitor the blood pressure values when amlodipine is taken with CYP3A4 inducers. (3)

FDA CYP3A4 Inducers Drugs List

Some of the commonly used medications that strongly induce CYP3A enzymes are:

Apalutamide,
Carbamazepine,
Dexamethasone,
Enzalutamide,
Fosphenytoin,
Lumacaftor and Ivacaftor,
Midostaurin,
Mitotane,
Phenobarbital,
Phenytoin,
Primidone,
Rifampin,
Rifamycin,
Rifapentine,
Rifaximin,
Rimexolone, and
St. John’s Wort. (12)

The first four drugs from the list above are strong inducers, while others have moderate or weak effects on enzyme activity, following the FDA categorization. (8)

The general recommendation is to avoid the concomitant usage of strong inducers with amlodipine or to use an alternate drug. (9)

3. Impact of Amlodipine on Other Drugs

While CYP3A4 inhibitors and inducers impact amlodipine availability and its therapeutic activity, amlodipine can also affect the activity of some drugs.

Simvastatin

One example of an interaction where amlodipine impacts drug activity is the concomitant use of amlodipine and simvastatin. Simvastatin is another medication used to reduce the risk of heart attack and stroke. It decreases cholesterol levels as well as stabilizes cholesterol plaques on artery walls. (3, 13)

When used together, amlodipine may increase the blood levels of simvastatin. This can lead to the following symptoms:

Muscle weakness,
cramps,
stiffness, and
spasms.

Higher levels of simvastatin increase the risk of muscle disease development (myopathy). Moreover, the damaged muscle may release its proteins and electrolytes into the blood, damaging the kidneys. Such damage can cause a serious medical condition called rhabdomyolysis which can cause disability or death. (3, 14, 15)

Cyclosporine and Tacrolimus

Amlodipine may increase the level of cyclosporine or tacrolimus when used together in people that genetically lack CYP3A5 enzymes. (16)

Cyclosporine and tacrolimus are immunosuppressants. These medications decrease the activity of the immune system and help the body accept the transplanted organ and not attack and reject it. (17-18)

The concomitant use of amlodipine with cyclosporine, and tacrolimus, results in systemic exposure to these two medications. That requires monitoring the blood’s cyclosporine and tacrolimus levels, and dose adjustment is recommended when necessary. (3)

Lofexidine

Some interactions may lead to a synergic effect, like in the case of lofexidine. Combining amlodipine and lofexidine increases the risk of excess lowering blood pressure or excessive bradycardia. (9)

It is recommended to read the Medication Guide before beginning the therapy and pay attention to any changes or adverse events that might occur. Some can be a result of amlodipine interactions.

Conclusion

Amlodipine may interact with certain medications that affect its therapeutic effects. For example, CYP3A4 inhibitors increase the clinical effect of amlodipine, while CYP3A4 inducers reduce it. Therefore, be aware of any changes in blood pressure control or the appearance of adverse events, and inform your doctor about any changes.

Aside from their effect on amlodipine, and vice versa, amlodipine may change their clinical effect. Therefore, tell your doctor all the medications you use. Follow the doctor’s recommendations and required monitoring that will ensure effective and safe therapy.

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Amlodipine Interactions with Other Medications

Summary