Amlodipine Interactions with Other Medications

Amlodipine Interactions Amlodipine Interactions

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.

Amlodipine Interactions – 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 narrowed arteries with 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 (e.g., ritonavir, ketoconazole, erythromycin, ranitidine, etc.) may increase the effect of amlodipine, while others, such as carbamazepine or phenobarbital, reduce the amlodipine levels in the blood and by that its clinical effect. (3)

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. CYP3A Inhibitors Increase Amlodipine Effect

Medications that inhibit the activity of CYP3A enzymes, so-called CYP3A inhibitors, increase amlodipine levels in the body and its antihypertensive effect.

CYP3A is an enzyme in the human body responsible for drug metabolism. It 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. (4-5)

The metabolism of amlodipine is held in the liver, where the active substance is transformed into inactive metabolites. (6) 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 CYP3A 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 therapeutic effect. (7)

Diltiazem

Co-administration with diltiazem 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. (8)

Food and Drug Administration CYP3A4 Inhibitors Drugs List

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

  • cobicistat,
  • itraconazole,
  • ketoconazole,
  • posaconazole,
  • telithromycin,
  • troleandomycin,
  • voriconazole. (7)

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

  • ciprofloxacin,
  • cyclosporine,
  • diltiazem,
  • erythromycin,
  • fluconazole,
  • imatinib,
  • verapamil,
  • cimetidine,
  • clotrimazole,
  • ranitidine,
  • ranolazine, etc.

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. (7)

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

2. CYP3A Inducers Decrease Amlodipine Effect

Another group of medications has the opposite effect on CYP3A enzymes; they induce the enzymes’ activity. These medications are called CYP3A inducers. If the drug supports the enzyme’s activity, it will increase the metabolism of amlodipine. (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 CYP3A inducers. (3)

FDA CYP3A4 Inducers Drugs List

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

  • carbamazepine,
  • enzalutamide,
  • phenytoin,
  • rifampin,
  • bosentan,
  • dabrafenib,
  • lorlatinib,
  • phenobarbital,
  • primidone,
  • armodafinil,
  • modafinil,
  • rufinamide, etc.

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. (7)

The general recommendation is to avoid the concomitant usage of strong inducers with amlodipine or to use an alternate drug. (8)

3. Impact of Amlodipine on Other Drugs

While CYP3A 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 the cholesterol built up on the walls of the arteries. (3, 9)

When used together, amlodipine increases the level of simvastatin. This leads to occurring the following symptoms:

  • 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 heart and kidneys. Such damage can cause a serious medical condition called rhabdomyolysis which can cause disability or death. (3, 10, 11)

Cyclosporine and Tacrolimus

Amlodipine may increase the level of cyclosporine or tacrolimus when used together.

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. (12-13)

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 lowering blood pressure or excessive bradycardia. (8)

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, CYP3A inhibitors increase the clinical effect of amlodipine, while CYP3A 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.

See Also

Pantoprazole Interactions

Metronidazol Interactions

Tramadol Contraindications

Tramadol Side Effects

Tramadol Interactions

What is Creatinine Level in Blood Tests?

Names of Blood Thinners

What is the Prescription Filling Process Between Doctors and Pharmacies?

References

  1. MedlinePlus, Amlodipine, 2021 Feb, https://medlineplus.gov/druginfo/meds/a692044.html
  2. National Library of Medicine, K. G. Bulsara, M, Cassagnol, Amlodipine, 2023 Jan, https://www.ncbi.nlm.nih.gov/books/NBK519508/
  3. Food and Drug Administration, KATERZIA (amlodipine) oral suspension, for oral use, 2019 Jul, https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211340s000lbl.pdf
  4. M. W. Shannon MD, Drug Interactions, Clinical Management of Poisoning and Drug Overdose (Fourth Edition), 2007 https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp3a
  5. M. Baader, U. A. Meyer, Cytochrome P450 Monooxygenase 3A4-5, xPharm: The Comprehensive Pharmacology Reference, 2007 https://www.sciencedirect.com/topics/medicine-and-dentistry/cyp3a
  6. National Library of Medicine, K. G. Bulsara, M, Cassagnol, Amlodipine, 2023 Jan, https://www.ncbi.nlm.nih.gov/books/NBK519508/
  7. Food and Drug Administration, Drug Development and Drug Interactions | Table of Substrates, Inhibitors and Inducers, 2022 Aug, https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table3-2
  8. Medscape, Amlodipine (Rx), Drugs and Diseases, https://reference.medscape.com/drug/katerzia-norvasc-amlodipine-342372#3
  9. MedlinePlus, Simvastatin, 2020 Jan, https://medlineplus.gov/druginfo/meds/a692030.html#:~:text=Simvastatin%20is%20in%20a%20class,other%20parts%20of%20the%20body.
  10. National Library of Medicine, H. Nagy and K. D. Veerapaneni, Myopathy, 2022 Aug, https://www.ncbi.nlm.nih.gov/books/NBK562290/#:~:text=Myopathy%20is%20derived%20from%20the,stiffness%2C%20cramps%2C%20and%20spasms.
  11. Centers for Disease Control and Prevention, Rhabdomyolysis, 2023 Feb, https://www.cdc.gov/niosh/topics/rhabdo/default.html#:~:text=Rhabdomyolysis%20(often%20called%20rhabdo)%20is,permanent%20disability%20or%20even%20death.
  12. MedlinePlus, Cyclosporine, 2015 Dec, https://medlineplus.gov/druginfo/meds/a601207.html
  13. MedlinePlus, Tacrolimus, 2023 Jan, https://medlineplus.gov/druginfo/meds/a601117.html#:~:text=Tacrolimus%20(Astagraf%20XL%2C%20Envarsus%20XR,have%20received%20a%20kidney%20transplant

About the Author

Biljana Srbinovska
Biljana is a Master of Pharmacy, with a Healthcare Management specialization. Over 20 years of professional engagement to enable access to innovative treatments for patients in need. Biljana is dedicated to upgrading health education evidence-based, promoting a healthy lifestyle, and embedding healthy habits.

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