Which Medicines Should Not Be Taken Together?

There are many drugs that interact and should not be taken together. These drug-drug interactions include nonsteroidal anti-inflammatory drugs (NSAIDs), antacids, decongestants, first-generation antihistamines, certain foods (grapefruit juice, dairy), herbal products and minerals, kava kava, iron (ferrous sulfate), warfarin, selective serotonin reuptake inhibitor (SSRIs) antidepressants, statins, and others.

Every medicine is processed by the body differently, and when medicines are taken together it can change the way they affect the body in what is called a drug-drug interaction. This can occur with both prescription and over-the-counter (OTC) medicines.  

The main types of drug-drug interactions are:

• Duplication
  • Taking two medicines with similar active ingredients together that may provide more medicine than needed
• Opposition
  • Medicines with active ingredients that have opposite effects on the body when taken together may reduce the effectiveness of one or both drugs
• Alteration
  • One medicine can change the way the body absorbs, spreads, or processes another medicine

List of Drugs That Interact

The following is a list of some common drug-drug interactions and medicines that should not be taken together. It is not a comprehensive list and does not include all possible interactions. To avoid potential drug-drug interactions, tell your doctor about all the medicines you take, including prescription medications, over-the-counter (OTC) drugs, herbal supplements, vitamins, and minerals. 

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • NSAIDs can reduce the effectiveness of some of the most common drugs used to treat high blood pressure (antihypertensives) and increase the risk for renal failure
    • Diuretics
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Angiotensin receptor blockers (ARBs)
    • Digoxin
  • NSAIDs can also interact with:
    • Lithium
    • Methotrexate
• Antacids 
  • Can affect the bioavailability of certain drugs by increasing gastric pH and may prevent many medications from being absorbed into the blood, which may result in a medication being less effective or not working at all
  • Antibiotics
  • Blood thinners
  • Heart medications
• Decongestants, such as dextromethorphan or pseudoephedrine
  • Frequently found in cold remedies, can cause harmful increases in blood pressure when taken with: 
    • Antihypertensive medications 
    • Monoamine oxidase inhibitors (MAOIs)
• First-generation antihistamines 
  • These have a sedative effect that can enhance the central nervous system depressant effects of a number of drugs
    • Alcohol
    • Benzodiazepines
    • Opiates
    • Barbiturates
    • Phenothiazines
       
• Certain foods
  • Grapefruit juice 
    • Interferes with drug metabolism which can increase drug levels in the body
      • Calcium-channel blockers such as amlodipine and felodipine
      • Some statins including simvastatin and lovastatin, and atorvastatin
      • Cyclosporine
      • Amlodipine
      • Nifedipine
  • Calcium-rich dairy products 
    • Can lessen the effectiveness of antibiotics, especially tetracycline
• Herbal products and minerals
  • St John's wort (Hypericum perforatum) can reduce the effectiveness of certain drugs and can cause:
    • Reduced cyclosporine concentrations resulting in transplant rejection
    • Serotonin syndrome when taken with selective serotonin reuptake inhibitor (SSRI) antidepressants
    • Unwanted pregnancies in women taking oral contraceptives
    • Reduced blood concentrations of antiretroviral drugs (indinavir, nevirapine) and a possible increase in resistance to these drugs
    • Reduced effectiveness of anticancer drugs (irinotecan, imatinib)
  • Ginkgo biloba 
    • Inhibits blood clotting and may cause problems if taken with:
      • Anticoagulants 
      • Blood thinners
      • Aspirin
  • Kava kava
    • Often taken to reduce stress, may have additive effects if it is taken with:
      • Muscle relaxants
      • Sedatives
      • Antidepressants
  • Iron (ferrous sulfate) 
    • Can negate the effects of the antibiotic tetracycline
• Histamine2 (H2)-receptor antagonists such as cimetidine and ranitidine
  • Can reduce the liver metabolism and increase plasma concentrations of many drugs, leading to toxicity
    • Phenytoin
    • Theophylline
    • Warfarin
    • Certain benzodiazepines
    • Sildenafil
  • Can reduce the bioavailability of certain drugs which may prevent many medications from being absorbed into the blood which may result in the medication being less effective or not working at all
    • Itraconazole
    • Ketoconazole
    • Cefditoren
    • Cefpodoxime
    • Cefuroxime
  • Can impair the renal elimination of certain drugs, resulting in toxicity
    • Procainamide 
    • Dofetilide
• Selective serotonin reuptake inhibitor (SSRIs) antidepressants
  • Serotonin syndrome, a potentially life-threatening condition, can be caused by an interaction between two serotonergic drugs that work by different mechanisms and may occur when an SSRI us taken with:
    • Serotonin/norepinephrine reuptake inhibitors (SNRIs)
    • Tramadol 
    • Trazodone
    • Dextromethorphan
    • Linezolid
• Statins (HMG-CoA reductase inhibitors), when taken with CYP3A4 inhibitors, can increase the risk of breakdown of muscle tissue (rhabdomyolysis)
  • The most common interactions occur with statins and:
    • Fibrates (especially gemfibrozil)
    • Azole antifungals
    • Amiodarone
    • Macrolide antibiotics (especially erythromycin and clarithromycin, but not azithromycin)
    • Protease inhibitors (e.g., ritonavir)
    • Calcium-channel blockers (especially verapamil and diltiazem)
• Clarithromycin 
  • The antibiotic clarithromycin can cause low blood pressure (hypotension) and acute renal failure when taken with certain calcium-channel blockers 
    • Amlodipine 
    • Felodipine
  • Serious drug-drug interactions can also occur when clarithromycin is taken with other drugs
    • Statins such as simvastatin or lovastatin
    • Colchicine
    • Glipizide or glyburide 
• Trimethoprim/sulfamethoxazole (TMP/SMX) 
  • Can cause high potassium levels (hyperkalemia) in elderly patients and those with chronic kidney disease when combined with
    • Angiotensin-converting enzyme (ACE) inhibitors
    • Angiotensin receptor blockers (ARBs)
• Warfarin
  • When combined with certain drugs it can increase the international normalized ratio (INR), which is a measurement of how long it takes blood to clot
    • Acetaminophen (Tylenol)
    • Prednisone
    • Trimethoprim/sulfamethoxazole (TMP/SMX) 
    • When warfarin is combined with nonsteroidal anti-inflammatory drugs (NSAIDs)
• Thyroid hormone and proton pump inhibitors
  • Many drugs can interfere with thyroid hormone absorption, causing patients to develop hypothyroidism (low thyroid levels)
    • Proton pump inhibitors (PPIs)
    • Statins
    • Iron
    • Calcium
    • Magnesium
    • Raloxifene
    • Estrogens