Medicine Side Effects and Interactions

COMMON MEDICATIONS: RISK VERSUS BENEFITS

The Good, the Bad, and the Ugly

Over-the-Counter medicines - Antibiotics - Decongestants - Generics - Supplements - NSAIDS - Corticosteroids - Statins - PPIs - Nicotine interactions - Aspirin - SSRIs - Medicine interference with lab tests - CYP 450 drug interactions

Many Medications Have Side Effects and Interactions

There are some medications, supplements, or substances you take because they fulfill a particular medical or mental need. Nearly all of these can have potentially unwanted or unusual side effects. When you take one of these, certain "risks versus benefits" should be

considered. Some of the more common of these are discussed below.

It may surprise you to know how many everyday prescription medicines, over-the-counter medicines, supplements and herbal remedies can cause side effects and have interactions with one another. If nothing else, READ LABELS (but they make that writing sooo small!!). If you feel your medication is not working, discuss it with a healthcare provider. If you think you got the wrong medicine, look it up. If you have severe side effects, go to urgent care or ER. If you suspect you may be having low-level, ongoing side effects, try not to discontinue your medication without contacting a healthcare provider to discuss the need for a substitute (especially medicines for blood pressure and mental health, seizures, and those medications you may need).

​​If you are on any of the following medications and suspect that you are having arrhythmias (chest pounding, fluttering, skipping, or a rapid heartbeat), discuss it ASAP with a healthcare provider, go to urgent care, or go to the ER if severe.

Some medications are more likely to have side effects than others. Some of these are included in the following discussion.

WHAT IS IN YOUR OVER-THE-COUNTER MEDICINE?

With a few exceptions, over-the-counter medicines can help make your symptoms go away but will not often treat the cause.

There are MANY cold medicines on the pharmacy shelves these days, and those shelves just get longer and longer with so many medications that it can be seriously mind-boggling. Many of those medications have a lot in common. In fact, a lot of them are the same ingredients but with a different name! Most contain three of the following:

• A fever reducer and/or pain killer - Tylenol (acetaminophen) or Motrin (ibuprofen) 

•  An antihistamine (chlorpheniramine, doxylamine, or diphenhydramine) for a runny nose/congestion (These may help decrease watery and itchy eyes, runny nose, postnasal drip and sneezing. They also tend to dry a person out too much!).One of these, Benadryl, works on cough centers as well.

•  A cough suppressant (dextromethorphan works on cough centers in the brain)

•  Guaifenesin (common: Mucinex) (only in a few cold preparations) - An "expectorant" that helps break up very thick mucus so a person can cough it up or blow it out of your sinus and cough it up.

•   A decongestant - Some have a "D," which is Sudafed (this has lots of potential side effects like high blood pressure, palpitations, and insomnia). Others have a decongestant in them called phenylephrine - Interestingly, recent reports that phenylephrine does NOT work for anything. Both of these medications also tend to dry a person out.

  
  

If you do not need all three components, you should think of treating your symptoms individually. For example, you have a fever? Treat it with Advil. Do you have a runny nose?Use an anti-histamine. You may not need all that other stuff like guaifenesin for thick mucus or dextromethorphan for a cough.

ANTIBIOTICS

Stomach Problems: Most antibiotics can cause diarrhea: It is not uncommon for me to get callbacks from patients about diarrhea when they are taking antibiotics. I find that the biggest culprits are Augmentin (amoxicillin-clavulanate), Clarithromycin (Biaxin), and erythromycin, but diarrhea and stomach problems can happen with any antibiotics. If this happens to you, call your healthcare provider. You can also take probiotics, if you are not immune-compromised, it is good to take them between your antibiotic doses to prevent stomach upset or if you begin getting symptoms. They will help put "good" bacteria back into your gut to keep things calm or help calm things down: Lactobacillus, L. rhamnosus, L. casei, and L. acidophilus. If you are unsure what to use, ask a pharmacist (and ask for the least expensive-these things get spendy!). 

Antibiotics: Clostridium-difficile ("C-diff"): Everyone has a little bit of C-diff bacteria in their gut, but antibiotics can cause an overgrowth, which, in turn, can cause a case of severe, sometimes life-threatening, watery diarrhea. Compromised immunity can also contribute to development of C-diff. C-diff is highly infectious. It spreads easily in medical and long-term care facilities. As far as antibiotics go, some of the most common culprits include clindamycin, cephalosporins (Omnicef, Rocephin), ciprofloxacin (Cipro), levofloxacin (Levaquin) and sometimes penicillins (especially amoxicillin-clavulanate/Augmentin. If you get watery diarrhea while taking (or after taking) an antibiotic, let a healthcare provider know.

C-diff can recur with later doses of antibiotics.

Antibiotic-related yeast infections: These infections can occur women and occasionally, during or right after taking an antibiotic. It's the same old story: Antibiotics kill harmful bacteria AND good bacteria. When the good bacteria die off, they can no longer protect you from yeast, which, in turn, overgrows. Viola! A yeast infection! It is characterized by intense genital itching and redness; there may be a whitish discharge from the vagina (or penis). The antibiotics that tend to cause this more are the following:

Augmentin (big perpetrator), Doxycycline, Cipro, Bactrim - broad-spectrum antibiotics capable of killing MORE - a bigger spectrum - of bacteria. "The bigger they come, the harder they fall".

OTHER NOTABLE SIDE EFFECTS OF VARIOUS ANTIBIOTICS

Fluoroquinolones:

• Levaquin has been a very effective antibiotic for many tough-to-treat infections. 

• Ciprofloxacin, another in the same family, has been widely used and effective in urinary tract infections. But after several years and much use, it has been discovered to cause joint pain (particularly knees, shoulder, and elbow) as well as muscle, and nervous system problems (peripheral neuropathy - numbness or tingling of extremities, twitching). People have developed cardiac (valve problems and heart irregularities like Q-T prolongation), tinnitus (ringing in the ears), eye problems, and, sometimes, people complain of memory problems. Side effects can last from days to, well...forever. There is a black box warning on the packaging of these medications.    

​Macrolides: 

• Zithromax can cause Q-T prolongation - heart arrhythmias

• Erythromycin can cause Q-T prolongation - cardiac arrhythmias, complaints of stomach problems are common with this drug

• Clarithromycin can cause heart arrhythmias, stomach problems

Sulfonamides (sulfa)

• Sulfamethoxazole/trimethoprim (Bactrim) - Often used for urinary tract infections and staph infections. A Rash is common while taking this medication or may occur several days after)

  
  

DECONGESTANTS​​​

Pseudoephedrine, Sudafed  or "D" products (i.e. Zyrtec D)

This is often a component of cold and allergy medicines. It is a very good decongestant that helps to temporarily clear sinus passages. However,  I often find, in my patients who take it that, that it increases blood pressure (sometimes significantly) and tends to cause restlessness,  insomnia, and, very occasionally, tachycardia (racing heart). Some people tolerate pseudoephedrine just fine, and actually like the stimulating effect. But others are very sensitive to it and all too often develop these side effects - especially high blood pressure – often without realizing it. If you have high blood pressure, it probably is wise to stay away from it. When you are ill, you really need to rest and do not be stimulated.

Occasionally, this nasal spray will dry you out so much that your mucus thickens, festers and can becomes a sinus infection.

Pseudoephedrine may help but be careful with it. ​​​​​​READ LABELS.

​​​​​​​​Afrin (oxymetazoline):

Afrin nasal spray (and similar spin-off nasal sprays containing oxymetazoline) is a nasal decongestant with an unusual reputation. It has immediate benefits for opening nasal passages, stopping postnasal drainage (which causes core throat and cough), and often helps with ear congestion (I learned from several of the airline attendants I have treated that Afrin is frequently used for ear pressure when they are ascending and descending during a flight). 

The great thing about Afrin is that it usually clears the sinus passages IMMEDIATELY (unlike the other steroid nasal sprays, which typically take a couple of days to optimally work). In addition, it is a decongestant. Most of it stays localized to the sinus area and causes far fewer systemic side effects than the other popular decongestant pseudoephedrine. Afrin does have a place in life. 

For those who "fear" Afrin, let me make one thing clear. Sometimes, when I recommend this nasal spray to patients, they give me some seriously nasty looks like I am trying to hurt then and exclaim, "But that's addictive!". Of course I am not trying to hurt anyone. Let me explain. If used for more than three days, it can cause rebound congestion which means that a person needs to keep using it to breathe out of their nose. This is called "rhinitis medicamentosa." Otherwise, it is not an "addiction." ResearchGate quotes the definition of addiction from the American Society of Addiction Medicine: "Addiction" is "a primary, chronic disease of brain reward, motivation, memory, and related circuitry." If used for too long it can cause damage to the nasal tissue. While overuse can be corrected in various ways, very simply: Don't use Afrin for more than three days! READ LABELS!

BLOOD PRESSURE MEDICATION

Lisinopril and the notorious cough. Do you have a cough that you can't get rid of? Check your medications. Lisinopril (and other ace inhibitors ending in "il" used for blood pressure), a very good blood pressure medication that has been around for a long time, is sometimes an unsuspecting culprit in an ongoing cough. I have seen where patients have been sent for chest X-rays and to pulmonologists when someone finally realizes it is the lisinopril causing the cough. If you think this may be occurring, speak to your healthcare provider. Other agents commonly known to cause an ongoing cough include fluticasone/Flonase nasal spray, simvastatin (Zocor), bisphosphonates (used for osteoporosis), Keppra, NSAIDS (common: ibuprofen /Motrin, Advil) or aspirin, beta-blockers (blood pressure medications ending in "olol")

SUPPLEMENTS

Should I Take a Lot of Supplemental Vitamins to Stay Healthy? There was a time when people thought that taking mega-doses of vitamins was an awesome thing to do - that high doses of vitamins would keep you alive forever. Not so - to the contrary. Yes, vitamins have their benefits, but it is best to use them as directed. The body gets rid of extra B and C vitamins in the urine. But the fat-soluble ones (A, D, E, and K) are stored in your fat and can become toxic. Sometimes, you may have side effects, or your liver enzymes will become elevated. Take recommended doses of vitamins or supplements according to your labs levels and your healthcare provider's recommendations. See the section on vitamins.

Grapefruit -Good or Bad?

Just a brief note about grapefruit: While grapefruit has many benefits, it may interact with some of your medications. In such cases, it can increase levels of some medications in your blood, which, in turn, can cause side effects. For example, grapefruit can cause an increase in circulating statins (taken for high cholesterol), calcium channel blockers (like amlodipine/ Norvasc, verapamil and others), anti-anxiety medications, corticosteroids, and cyclosporine drugs (anti-rejection medication). If you take any of these medications, it would be smart to avoid grapefruit (or get advice from your healthcare provider).

ARE GENERIC MEDICATIONS ANY GOOD?

Are generics a good replacement for name-brand medications? Yes. Usually. Most generics are fine. According to sources at Harvard Health, the FDA ensures that a generic drug is equivalent to the brand drug in quality, purity, stability, dosage, and strength before authorizing its use in the market. The FDA requires that the active ingredient of the generic (the" working ingredient") cannot have more than a 20% difference from the brand name's bioavailability. The FDA estimates that most generics actually have only an approximate 3.5% difference in absorption rates of active ingredients. Medication ingredients also include "fillers," which are inactive ingredients like binders, flavoring, preservatives, and food colorings. The fillers in generics are not required to match the brand name fillers. Some people

​ may be reactive to the fillers of generics.

Pharmaceutical companies can usually match active ingredients very well; however, with some medications, they have trouble making a good standardized generic. In those cases, you probably want to stick with brand names. The most common of these are thyroid medications, extended-release seizure meds, and blood thinners. Occasionally, a person cannot tolerate the different filler(s). Otherwise be aware that the brand name is often not better, and the generic is almost always cheaper. The generic and brand-name medications usually look different. But if your medication looks different than the last prescription refill, question it, always question it: Pill identifier from Drugs.com.​

NON-STEROIDAL ANTIINFLAMMATORIES

​"My healthcare provider told me not to take anti-inflammatories (NSAIDs) like ibuprofen (Motrin, Advil), Naproxen, and Diclofenac because I have high blood pressure." What do you think?? One or two doses of an anti-inflammatory typically only raises a person's systolic (top number) blood pressure by about 2-3 points. If your healthcare provider feels that those 2-3 points are going to be a game-changer for your blood pressure, then you must be riding a very thin line with your hypertension (that is, it must be pretty high). Anti-inflammatories do not normally raise blood pressure in someone who does not have high blood pressure. If you take the anti-inflammatory for a day or two and your blood pressure goes up a bit, it is expected to come down again. If it goes up to 160/100, stop taking the anti-inflammatory. Take Tylenol Extra Strength instead (if you can tolerate it).

On the other hand, taking NSAIDs on a daily basis - especially at higher doses - can and does cause chronically high blood pressure because, over time, NSAIDs can damage kidneys. Simply stated, kidneys play a significant role in regulating your blood pressure (among many other things). You don't want to mess with your kidneys!

CORTICOSTEROIDS (prednisone, dexamethazone)

As a healthcare provider, I have a love-hate relationship with the drug prednisone. It is a prescription medication, a corticosteroid, similar to the chemical your body produces (cortisol), which controls many metabolic processes and inflammatory conditions. It is probably one of the best anti-inflammatories there is.

Healthcare providers like to reserve corticosteroids for more severe cases of inflammation, for lungs (severe cough/asthma), excessive throat pain (and difficulty swallowing), allergies, rashes (including poison ivy), musculoskeletal pain due to inflammation, some gastric disturbances (Crohn's) and a number of other medical problems. 

While this is an excellent medicine for inflammation, there are a lot of potential problems with it: It can cause a transient increase in blood pressure and blood sugar so that it can be potentially harmful for those with hypertension and diabetes. It can cause insomnia (if taken too close to bedtime), mood problems, "roid rage" (anger), anxiety, sometimes psychosis (usually with people who have preexisting mental health problems), gastric ulcers, and bleeding, skin flushing and sweating, and it can increase hunger and fluid retention. One of the more worrisome side effects of corticosteroids is that, while decreasing inflammation, it can also weaken the immune system and reduce resistance (some people even develop shingles when they are on steroids!). While steroids can cause all of these problems, some people like to take them because they tend to give them energy (wrong reason to take steroids!). 

The benefits often outweigh the risks because low-dose corticosteroids work so well to decrease inflammation. Side effects, if present, are usually transient and come to pass unless taken long-term. Corticosteroids do have a bad reputation because of isolated incidents such as those mentioned above and because long-term use often causes chronic diabetes, cataracts, thinning of the skin, "moon face," osteoporosis, acne,  and vision problems. The list goes on. But it DOES decrease inflammation.​​ By the way, corticosteroids can also cause a yeast infection or make one worse because they increase a person's glucose levels (yeast loves sugar) and lower immunity.

STATINS

Trouble with statins? Sometimes, cholesterol medications, "statins," can cause some muscle aches and pains, myositis, and very rarely, rhabdomyolysis. Additionally, they can increase liver enzymes. I have met patients who come off their cholesterol medicine, because of this, with no substitute. If your healthcare provider feels you should be on cholesterol medications, you should be on something for cholesterol. Fat deposits from excess LDL and triglycerides start lining arteries - they get clogged, or plaques fly off the walls and cause problems elsewhere (i.e., the brain, the lungs). Cholesterol is a silent killer. ​

Patients report that CoQ10 sometimes helps with muscle aches secondary to statins. Maybe try adding that. If you are suffering severe side effects stop taking it and speak to your healthcare provider. Or if your liver enzymes are elevated, discuss alternatives with your healthcare provider. There are plenty of possible options to try.​

PROTEIN PUMP INHIBITORS (used for acid reflux and heartburn)

Are there problems with long-term protein pump inhibitors (PPI's)? These are the popular reflux/antiacid medications. Many people take them for reflux (GERD). Medications like omeprazole (Prilosec), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex) and esomeprazole (Nexium). You are supposed to take these ONLY for four to eight weeks and then wean off them. Long-term use of a PPI can cause long-term side effects: less calcium absorption with subsequent bone loss and increased fractures; pneumonitis (pneumonia type illness), c-diff risk, iron, magnesium, and B12 deficiency, heart problems, dementia, kidney problems, and gastric cancer although serious side effects are considered pretty rare.

Also, the PPIs have the potential to interact with and interfere with the actions of many, many other drugs. According to Drugwatch.com,  PPIs can interact with nearly 290 different medications, some of which are common. They can do this in many ways: They can directly bind with other medications, affect medicine absorption in the stomach, and compete with the receptors (CYP 450 2C19 and CYP 3A4 metabolized drugs - below) that other medications are metabolized by. One action which may help (to some degree) is to space your PPIs apart from your other medications by several hours.  

Also, if you feel you need to take stomach medicines for a while, consider alternating between a PPI and an H2 inhibitor (common: Pepcid). They are different classes of medications so are less likely to cause long-term effects. Change your health habits. Evaluate your diet - what is it that triggers your reflux? Keep a diary. Try to eliminate those things or at least slow down on them. And, change some lifestyle habits: don't lay down after meals; stop eating fatty and spicy foods and chocolate; slow down on the coffee, alcohol, and energy drinks; make your meals smaller; elevate the head of your bed on blocks three to four inches. Please read about it. Talk to your healthcare provider about it. Long-term issues with stomach acid and GERD can cause serious problems.

THE DEBATE ABOUT ASPIRIN

Aspirin – To take a daily dose or not to take it. That is the question. This decision is a "risk versus benefits" situation. Note: if your healthcare provider tells you to take aspirin daily (unless you have an ulcer or active bleeding). Your provider knows your history. If, after reading this, you have any questions, discuss them with your medical professional. I know plenty of people who take a baby aspirin, not because their healthcare provider recommends it but because they have heard that "it is good for you". It really depends on your health history and sometimes your family history. Here is a brief breakdown.

​Surprisingly, aspirin does thin your blood - even a tiny 81 mg baby aspirin is quite effective, so you will bleed and bruise more easily. 

Let's look at the risks versus benefits:

RISKS:

• Aspirin can make you bleed - Anywhere from the stomach to the brain to the nose-anywhere. It is especially risky for those who have had stomach ulcers and stroke due to brain bleed.

• Asthma-Aspirin can make asthma worse.

• Excessive alcohol use (more than three drinks/day). Those who use alcohol excessively are at risk for gastrointestinal bleeding if they take aspirin.

• People 70 years or older (except those with cardiovascular disease) - because older people have more of a tendency to bleed than younger ones do.

• Taking other NSAIDs like ibuprofen (i.e., Motrin, Advil), Naproxen, Diclofenac, and even oral steroids)increases the chance of a gastrointestinal bleed.

•  Uncontrolled high blood pressure - Aspirin can affect your kidneys adversely. Kidneys help regulate blood pressure.

• Kidney disease - Can make it worse.

• Trauma- Bleeding risk

• Do not take aspirin if you are taking other blood thinners (e.g., Plavix, Coumadin, Eliquis, Xarelto) unless your healthcare provider advises you to do so.

• DO NOT GIVE TO KIDS UNDER 16 - (SOME SOURCES RECOMMEND NOT TO GIVE IN THOSE YOUNGER THAN 19 YEARS OLD) - especially in a child with a viral illness. Aspirin can cause Reyes Syndrome - a serious neurological condition.

​​​BENEFITS:

• It has anti-clotting effects and can keep a person from having a clot-related stroke, pulmonary embolus (clot to lungs) or clot to the heart (heart attack).

• Prevention if you have had a heart attack or are at risk for one. 

• Prevention for those with a family history of a heart attack - especially if those in your family have had a heart attack at a young age.

• A history of Thrombotic stroke (stroke caused by blood clot[s])

• If you have been told you have atrial fibrillation ("a-fib") - you should talk to your healthcare provider about this if you are not on aspirin or another blood thinner.

• Family history of gastric cancer (1)

• Prevention for those who have a history of blood clots or pulmonary embolism (blood clots to your lungs)

It is best to discuss the use of aspirin with a healthcare provider who can help you weigh the pros and cons of taking aspirin daily. It can be a tricky decision.

SMOKING/VAPING CAN CHANGE MEDICATION LEVELS IN THE BODY 

Did you know that smoking and vaping can increase or decrease the effects of certain medications you are taking? So be careful if you are on medications, and consider changing your smoking habits! Smoking and vaping (specifically polycyclic aromatic hydrocarbons or "PAHS") can increase the rate at which you metabolize, inactivate, or basically "get rid" of a medication in your bloodstream. So, if you suddenly start smoking, your body will start getting rid of your medicine faster. It will be less effective. If you quit smoking, your body will have more of the medication floating around in your bloodstream, so you may feel the effects more (it has to do with the CYP enzymes 1A2, 2B6, and 3A4- below - but don't let this confuse you). Several medications of greater concern here include Clozapine (Clozaril) and olanzapine (Zyprexa), methadone, warfarin (Coumadin), fluvoxamine (Fluvox), mirtazapine (Remeron), trazodone, duloxetine (Cymbalta), amitriptyline, escitalopram (Lexapro), benzos, and others.

So, maybe if you want these medications to work better, you might quit smoking or vaping. Actually, we would love you to quit but the idea here is just to be aware that your smoking can affect how your medications are working. If you suddenly decide to start smoking or vaping (please don't) or if you suddenly quit, you might expect a change in how you feel and how your medications are working (sometimes significant). You may want to discuss a dosage change with your healthcare provider if this occurs.

​SSRI INTERACTION WITH DEXTROMETHORPHAN ]-  "DM" (OTC Cough Medicine)

Depressed and have a cough? You would never think of this, but if you are on an SSRI (common: escitalopram/Lexapro, Celexa/citalopram, fluoxetine/Prozac, paroxetine/Paxil, sertraline/Zoloft, vilazodone/Viibryd) to increase your serotonin level to brighten up your mood, and you take the over-the-counter cough medicine, dextromethorphan (common: Delsym, some Robitussin products, "DM" products) your chance of developing serotonin syndrome increases. Dextromethorphan increases serotonin levels by acting like an SSRI (inhibits reuptake of serotonin) and also it blocks serotonin from leaving your body (dextromethorphan blocks metabolism of the SSRI at CYP2D6). The accumulation of serotonin in your bloodstream can cause symptoms like anxiety, agitation, confusion, sweating, fever, high blood pressure, seizures, and others. If you are on an SSRI, do not take excessive doses of dextromethorphan, no matter how bad your cough is. In excess doses, dextromethorphan can cause some unusual side effects. In some countries, it is available only by prescription and in a few other countries it is actually banned because it is considered an illicit drug used for recreational use.

Medications Than Can Interfere with Lab Tests

If you have lab work done, you might want to remind your healthcare provider  (or anyone interpreting your labs) if you are on the following medications:

• B vitamins: Especially Biotin (vitamin B7). Troponin levels are often used as a marker for a heart attack. If someone is having a heart attack and taking B7, troponin blood levels may appear to be low. False results can also occur with testosterone, estradiol, cortisol, free triiodothyronine (T3), and free thyroxine (T4) levels. Biotin can also cause erroneous results in thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone, parathyroid hormone, and human chorionic gonadotropin levels. It can cause results of falsely high levels of IgE and falsely low levels of insulin, autoantibodies, vitamin B12, vitamin D, folate, prostate-specific antigen, carcinoembryonic antigen, thyroglobulin, ferritin, DHEA-S, IgM, and hepatitis A, B, and C antibodies, falsely elevated levels of IgE and falsely low levels of insulin, changes in autoantibodies, vitamin B12, vitamin D, folate, prostate-specific antigen (possible slight elevation), carcinoembryonic antigen, thyroglobulin, ferritin, DHEA-S, IgM, and hepatitis A, B, and C antibodies. 

• (PPIs) such as omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, and esomeprazole can cause false negatives in the urea breath test and the stool antigen test. PPIs and coumadin can cause increased INR and PT

• Cephalosporins can cause false positive results in urine glucose

• Amiodarone, NSAIDS, Propranolol -false levels of PT/INR

• Gabapentin, Chloroquine and quinine - False elevation of proteinuria

• Tylenol: False high reading on some continuous glucose monitors

• Penicillin-type antibiotics like amoxicillin and ampicillin can also cause falsely elevated glucose test results.

• NAC-Low Creatinine, low HDL, falsely low triglycerides, low uric acid,

• Cefoxitin-Low creatinine

• DHEA-High progesterone

• ​Some antidepressants, antipsychotics, anti-dyskinesia agents, and antihistamines like Benadryl, HIV meds, NSAIDS, dextromethorphan, and diet pills can cause false positives on drug screens and in pregnancy tests (1).

• Prednisone-May effect cortisol

• 
  

• Sulfasalazine - ALT

• Fluorescein (eye drop at ophthalmologist sometimes) - CA125, TSH low, high vitamin D

• Media Contrast (often used in X-rays, CT scans, and MRIs) can affect calcium and zinc lab results. These agents can also cause positive interference in creatinine, magnesium, selenium, and total iron binding capacity assays and interference in iron assays.

• For more information, check MDLinx.

CYP450 - POTENTIAL INTERACTIONS OF MEDICATION

​​The following is a discussion about drugs metabolized by some major CYP450 enzymes. Reading and comprehension are a bit labor intensive unless you are used to reading about and/or studying this information. Still, it helps understand why some medications, supplements, herbals, and even certain foods may not work well when taken together. There may be an increase or decrease in how one of your medications works: sometimes a major one and sometimes a minor one.

Some interactions are very weak, and some are very strong. There is still much research to be done in this area.  

You must watch for medication interactions carefully, whether it is prescription medicines, herbs, or supplements. CYP450 enzymes can induce or inhibit drug metabolism.

Medications are eliminated from your body mainly by CYP 450 receptors, which are primarily in the liver but also in other organs (especially the small intestine). When you take one medication that is metabolized through one receptor, and a second medication comes along to ”sit“ on the same receptor, they may compete for use on the same receptor. One can regulate the metabolism of the other: It can control whether the other drug gets metabolized (and eliminated from the body) too fast or too slow. One may be eliminated from your body too fast, and not enough circulates in the bloodstream, or it gets eliminated too slowly, and it builds up in your bloodstream, and you get too much (respectively). So, one drug may affect the concentration of another drug in your body.

A brief vocabulary check: Substrates are the drugs being eliminated by sites on the CYP enzyme (P450). Inducers, basically, cause a drug to be eliminated faster from the body, so it may not work as well. Inhibitors slow the metabolism of the drug on the receptor-they block it so your body does not get rid of it fast enough, and there may be so much in your body that it can cause side effects (they inhibit metabolism not the action of the drug as one might think). Interestingly, an inhibitor can sometimes be an inducer or substrate and vice versa.

Again, it is important to note that some of these are minimal or potential interactions and some may be significant. Check carefully for interactions  f you take a substrate with either with an inhibitor or inducer. If you see an interaction, discuss it with your healthcare provider or a pharmacist

Those highlighted medications, supplements, foodstuffs and herbs are amongst some of the more commonly used ones.

CYP1A1

·       Substrate: Theophylline is a drug that is normally metabolized and eliminated at the CYP450 CYP1A1 site.

·       Inhibitors:(These drugs will slow the elimination of theophylline so you  have more circulating around your body, and it can become toxic): Turmeric/curcumin, German chamomile, peppermint, dandelion, echinacea,  kava, St John’s Wort, caffeine, Tagamet, citalopram, echinacea, fluoroquinolones, Fluvox, isoniazid, lime, sweet orange.

·       Inducers: (These will cause the drug Theophylline to be metabolized too quickly so it will not be as effective):  Broccoli, Brussel sprouts, cauliflower, Provigil, omeprazole (Prilosec), Dilantin, tobacco.

​​CYP1A2

·       Substrates: Quite a few medications normally metabolized and eliminated by the receptor CYP1A2 include: Clozapine (Clozaril), cyclobenzaprine (Flexeril), fluvoxamine (Luvox), haloperidol (Haldol), imipramine (Tofranil), mexiletine (Mexitil), olanzapine (Zyprexa), pentazocine (Talwin), propranolol (Inderal), tacrine (Cognex), theophylline, zolmitriptan (Zomig), warfarin/Coumadin, triamterene, Tizanidine (Zanaflex), propranolol (Inderal), and estradiol, caffeine, naproxen, duloxetine, amitriptyline, Zyprexa (olanzapine), imipramine, rutin, melatonin and others.

·       Inhibitors: A lot of medications can slow the metabolism of the substrates above and leave more of that substrate circulating in your body. Some inhibitors include: Black cohosh, cimetidine, fluoroquinolones (common: ciprofloxacin [cipro], citalopram (Celexa), erythromycin, Fluvoxamine, quercetin (mild), black cohosh (mild), ginseng (mid), green tea (high), grape seed extract (high), primrose, echinacea (weak), grapefruit juice, Kava, coriander, cumin, parsley, licorice, St John’s Wort, oral contraceptives, acyclovir, allopurinol, piperine (black pepper), cannabidiol (possible).

·       Inducers: These medications will increase the elimination of medications from your body so there may not be enough to do the job: Brussels, broccoli, tobacco, carbamazepine (Tegretol), omeprazole (Prilosec), rifampin, Dilantin, phenobarbital, echinacea, ginkgo, ritonavir, lansoprazole, tobacco/nicotine.

CYP2B6-

·       Substrates: The following are some of the medications normally metabolized on the CYP2B6 receptor: Bupropion (Wellbutrin), ketamine, Demerol, methadone, propofol, tramadol, selegiline, tamoxifen, valproic acid, nicotine, temazepam (Restoril), methadone.

·       Inhibitors: The following may slow the metabolism and the elimination of the CYP2B6 substrates (above) so you may have more in your system: Clopidogrel (Plavix), licorice, cumin, ashwagandha, mugwort/wormwood, selegiline (also substrate), "azoles" (antifungals), Prozac, green tea

·       Inducer: These cause a faster elimination of the CYP2D6 substrates (above) from your body: Carbamazepine (Tegretol), phenobarbital, Dilantin, rifampin, tobacco/nicotine.

CYP2C8

·       Substrate: The following are metabolized and eliminated on the CYP2C8 receptors: Pioglitazone (Actos) - The TZD family (“glitazones” for diabetes), chloroquine, buprenorphine, 

·       Inhibitors: The following are some medications that inhibit the metabolism of those substrates and cause more to circulate in your system: Gemfibrozil, montelukast/Singulair, Quercetin, trimethoprim (an ingredient of Bactrim), Plavix, NEEM, Gingko, Devils Claw.

·       Inducer: These may cause more rapid elimination of the substrate medications: Rifampin.

​CYP2C9

·       Substrates: Lots of these medications are metabolized on (and eliminated through) the CYP2C9 substrate: A lot of NSAIDS (ibuprofen/Motrin/Advil, naproxen, aspirin, meloxicam, Celebrex, diclofenac, indomethacin, ketoprofen), amitriptyline/Elavil, Plavix, doxepin, fluoxetine (Prozac), Fluvastatin, glimepiride, glipizide, glyburide, losartan (Cozaar), Dilantin, warfarin/coumadin, valproic acid, venlafaxine (Effexor), progesterone, alprazolam (Xanax), tamoxifen, lansoprazole (Prevacid), omeprazole (Prilosec), sildenafil (Viagra), montelukast (Singular), sulfamethoxazole (component of Bactrim), sertraline (Zoloft), melatonin, phenobarbital, valium, terbinafine, azelastine (Astelin), diphenhydramine (Benadryl), ketamine, donepezil, zolpidem (Ambien), caffeine, dextromethorphan, bupropion (Wellbutrin), diltiazem, estradiol, haloperidol (Haldol), nicotine, ondansetron (Zofran), methadone, selegiline, temazepam (Restoril), testosterone, cannabidiol (medical, cannabis).

·       Inhibitors: There are plenty of medicines, herbs, and fruits that inhibit the metabolism of the CYP2C9, so there tends to be more substrate acting in the body. These include Fenofibrate, ), Fluvastatin, lovastatin, Fluvoxamine (Luvox), metronidazole (an antibiotic related to antifungals), isoniazid, quercetin, "azole" antifungals like fluconazole (Diflucan), St John's wort, grapefruit juice, ginkgo biloba, black pepper, and echinacea, kava, modafinil, paroxetine (Paxil), promethazine, (Phenergan), sertraline (Zoloft), valproic acid, NEEM, licorice, garlic, cranberry, ginseng, cumin, epinephrine, methimazole, primrose, CBD, cinnamon, black pepper, (peperine), white pepper, ginger, nutmeg, devils claw, clary sage, oregano, eucalyptus, goldenseal, grapeseed extract, green tea, milk thistle, saw palmetto, soy, turmeric, black cohosh and mace, among others.

·       Inducer: Carbamazepine (Tegretol), phenobarbital, Dilantin/ phenytoin, rifampin, St John’s wort, dexamethasone.

​CYP2C19

·       Substrates: These medications are metabolized by the CYP2C19 receptor after which most are eliminated from the body: Amitriptyline (Elavil), carisoprodol (Soma), citalopram (Celexa), diazepam (Valium), PPI’s like lansoprazole (Prevacid), omeprazole (Prilosec), phenytoin (Dilantin), warfarin (Coumadin), atomoxetine (Strattera), chloramphenicol, clomipramine, Plavix, doxepin, escitalopram (Lexapro). labetalol, propranolol, valproic acid, venlafaxine (Effexor), vilazodone(Viibryd).

·       Inhibitors: These medicines inhibit the metabolism of the following medicines so there may be more of the substrate working in the body: cimetidine (Tagamet), quercetin, "azoles" (antifungals like Diflucan), citalopram (Celexa), fluoxetine (Prozac), indomethacin, kava, modafinil, probenecid, andrographis, black pepper, echinacea, ginkgo, St Johns wort, grapefruit, PPIs (proton pump inhibitors), topiramate (Topamax), black cohosh, devils claw, eucalyptus, evening primrose, garlic, Kava, milk thistle.

·       Inducers: These will increase metabolism of the CYP2C19 substrates so there will be less available in the body: Aspirin, carbamazepine (Tegretol), phenytoin (Dilantin), prednisone, rifampin, St Johns wort, and valerian.

CYP2D6 

·       Substrates: There are a lot of psych medications that are substrates metabolized by the CYP2D6 receptor so be careful if you take an inhibitor or inducer at the same time. These include amitriptyline (Elavil), amphetamines, aripiprazole (Abilify), atomoxetine, cariprazine (Vraylar), brexpiprazole (Rexulti), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), oxycodone,  fluoxetine (Prozac), meperidine (Demerol), methadone, Beta-blockers: carvedilol, propranolol, metoprolol, nebivolol,  (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), chlorpheniramine, chlorpromazine, (paroxetine(Paxil), risperidone (Risperdal), tamoxifen, imipramine, nortriptyline, citalopram (Celexa), clonidine, dextromethorphan (DM), doxepin, duloxetine (Cymbalta), escitalopram (Lexapro), fluvoxamine, Paxlovid

·       Inhibitors: Bupropion, cannabidiol, celecoxib, chlorpheniramine, chlorpromazine, cimetidine (Tagamet), citalopram (Celexa), clomipramine, diphenhydramine (Benadryl), doxepin, hydroxyzine (Atarax), St Johns wort, kava, methadone, vitamin B3 (niacin), omeprazole (Prilosec), paroxetine (Paxil), perphenazine, risperidone (Risperdal), ritonavir, sertraline (Zoloft), terbinafine (Lamisil), thioridazine (Mellaril), black cohosh, piperine (black pepper), devils claw, goldenseal, echinacea, kava, haloperidol (Haldol), eucalyptus, evening primrose, ginkgo, ginger, milk thistle, caffeine, berberine, sage, grapefruit, grapeseed extract, green tea, ​saw palmetto (minimal), soy, black cohosh

·       Inducers: Dexamethasone, prednisone, rifampin, red ginseng (weak)

​​CYP2E1

·       Substrates: Some substances that are metabolized on the CYP2E1 include: Alcohol, nicotine, acetaminophen (Tylenol), aspartame(sugar substitute), phenobarbital, ondansetron (Zofran), theophylline, isoniazid, carvedilol, caffeine, bupropion (Wellbutrin), sildenafil (Viagra), tamoxifen, iloperidone, capsaicin (pepper), theobromine, sertraline (Zoloft), phenytoin (Dilantin), ivermectin, cannabidiol, medical cannabis, tretinoin, Lunesta.

·       Inhibitors: These inhibit the metabolism of the substrate and cause higher levels of the substrate medicines to increase in the body: Disulfiram, garlic, miconazole, echinacea, goldenseal, ginkgo, St Johns wort, black pepper, grapefruit, ginseng, kava, resveratrol, isosorbide dinitrate.

·       Inducers: These inducers cause faster metabolism of the substrate and elimination, so there is less of that medicine available to the body: Alcohol (can act as an inducer or a substrate here), St Johns wort, tobacco, benzene.

CYP3A4 

Lots of activity by this enzyme – It breaks down 60% of prescription drugs. Because of this, some of the more common ones are addressed in the following:

·    Substrates:

      Many chemotherapeutic agents.

          Antifungals: Ketoconazole, itraconazole

          Antibiotics: Clarithromycin (Biaxin), erythromycin,

          Antidepressants and anti-anxiety medications: Amitriptyline (Elavil), citalopram

              (Celexa), clomipramine, imipramine, sertraline (Zoloft),

              Mirtazapine (Remeron), venlafaxine (Effexor), trazodone, vilazodone (Viibryd),  

              buspirone (Buspar)

         Antipsychotics: haloperidol (Haldol), aripiprazole (Abilify), risperidone  

              (Risperdal), ziprasidone (Zyprexa), ​quetiapine (Seroquel), Lurasidone (Latuda)

          Opioids: Buprenorphine, codeine, fentanyl,  hydrocodone, tramadol, methadone

          Benzodiazepines: Alprazolam (Xanax), triazolam (Halcion), diazepam (Valium),    

              clonazepam (Klonopin)​​, lorazepam (Ativan)

          Hormones: Some contraceptives,  estrogens, progesterone, testosterone,

          Antihistamines: Loratadine (Claritin)

          Antivirals and Immunosuppressive drugs – many -  including a component of  

             Paxlovid 

          Others: Cyclobenzaprine (Flexeril), Ambien, Statins (except pravastatin and    

             rosuvastatin, tamoxifen, calcium channel blockers (like amlodipine), sildenafil

   (Viagra), ​tadalafil (Cialis), finasteride (Propecia), glucocorticoids, budesonide        

   (Pulmicort), salmeterol (Serevent), hydrocortisone, dexamethasone, Fluticasone             (Flovent, Flonase), Ketofen, chlorpheniramine, Restasis, caffeine,

           dextromethorphan (DM), ondansetron (Zofran), cocaine, Propranolol, Warfarin,

Omeprazole  (Coumadin), clopidogrel (Plavix), Omeprazole (PPI-Prilosec), montelukast (Singulair), losartan, 

·      Inhibitors: The following will decrease metabolism and elimination and will increase the

concentration of the substrate

Antiviral: Paxlovid, some protease inhibitors (antiretrovirals),

Antibiotics: clarithromycin (Biaxin) and Erythromycin, chloramphenicol, ciprofloxacin (Cipro), (moderate), cyclosporine, azithromycin (Zithromax) (mild),

Antifungals: “azole” antifungals - Fluconazole (Diflucan), Ketoconazole, Itraconazole. (Significant reactions with these antifungals).

Others: verapamil, diltiazem, buprenorphine, cimetidine (Tagamet), omeprazole (Prilosec), ranitidine (Zantac), valproic acid (Depakote), amlodipine, isoniazid

Herbs/foods/supplements: Green tea extract (?), grape seed extract, dill, celery,  lime, lemon, parsley, chamomile, rutin wormwood/mugwort, grapefruit, valerian, berberine, quercetin, cannabidiol, star fruit, milk thistle, niacin, milk thistle, ginkgo (strong), ginseng (inhibitor and inducer), garlic, lemongrass, kava (mild inhibitor and inducer), pomegranate, licorice, eucalyptus, goldenseal, NEEM, licorice root, saw palmetto, resveratrol, curcumin, black pepper, CBD, red clover, echinacea (inducer           and inhibitor), oregano, cats claw, soy, devils claw, common sage (fairly strong) evening primrose, feverfew, black cohosh, cranberry (weak), neem, piperine (black pepper), white pepper, black elderberry, nutmeg, fennel, ginger, horsetail, and ginger, coltsfoot​​​, turmeric, cinnamon, and mace, and zinc, among others.

·       ​Inducers: The following will increase metabolism so the body eliminates the substrate medication more quickly, resulting in less available drug:  Carbamazepine, phenobarbital, phenytoin, rifampicin, oxcarbazepine (Trileptal), topiramate (Topamax), phenobarbital,  St. John's Wort and glucocorticoids, modafinil, capsaicin, echinacea (inducer and inhibitor), milk thistle, ginseng (inhibitor and inducer), kava inhibitor and inducer), butterbur​​​​​, black cohosh, gingko, and goldenseal.

Several sites have tables which list the various substrates, inhibitors and inducers: An inclusive list from Wikipedia is included here (always double check, as Wikipedia is not supposed to be used as reference but this is one of the best lists I have come across). Some of these interactions are negligible and depend on the circumstance - for example how much of a medication you are taking but some interactions can be severe. Some websites actually do list the most severe of the CYP450 interactions. Medications with severe interactions often have a warning label on them "do not take with...". If you are in doubt, ask a pharmacist. They have a great wealth of knowledge at their fingertips.