Drug Interaction; Types, Prevention, Complication

Drug interaction








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Drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together. This action can be synergistic (when the drug’s effect is increased) or antagonistic (when the drug’s effect is decreased) or a new effect can be produced that neither produces on its own. Typically, interactions between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and medicinal plants or herbs (drug-plant interactions). People taking antidepressant drugs such as monoamine oxidase inhibitors should not take food containing tyramine as hypertensive crisis may occur (an example of a drug-food interaction). These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.

Types of Drug Interactions

Pharmacodynamic interactions

  • The change in an organism’s response to the administration of a drug is an important factor in pharmacodynamic interactions. These changes are extraordinarily difficult to classify given the wide variety of modes of action that exist and the fact that many drugs can cause their effect through a number of different mechanisms. This wide diversity also means that, in all but the most obvious cases, it is important to investigate and understand these mechanisms. The well-founded suspicion exists that there are more unknown interactions than known ones.
  • Effects of the competitive inhibition of an agonist by increases in the concentration of an antagonist. A drugs potency can be affected (the response curve shifted to the right) by the presence of an antagonistic interaction. pA2 known as the Schild representation, a mathematical model of the agonist-antagonist relationship or vice versa.

Pharmacodynamic interactions can occur on

Pharmacological receptors – Receptor interactions are the most easily defined, but they are also the most common. From a pharmacodynamic perspective, two drugs can be considered to be:

Homodynamic if they act on the same receptor. They, in turn, can be

  • Pure agonists –  if they bind to the main focus of the receptor, causing a similar effect to that of the main drug.
  • Partial agonists – if, on binding to one of the receptor’s secondary loci, they have the same effect as the main drag, but with a lower intensity.

Antagonists – if they bind directly to the receptor’s main locus but their effect is opposite to that of the main drug. These include:

  • Competitive antagonists – if they compete with the main drug to bind with the receptor. The amount of antagonist or main drug that binds with the receptor will depend on the concentrations of each one in the plasma.
  • Uncompetitive antagonists – when the antagonist binds to the receptor irreversibly and is not released until the receptor is saturated. In principle, the quantity of antagonist and agonist that binds to the receptor will depend on their concentrations. However, the presence of the antagonist will cause the main drug to be released from the receptor regardless of the main drug’s concentration, therefore all the receptors will eventually become occupied by the antagonist.
  • Heterodynamic competitors – if they act on distinct receptors.

Signal transduction mechanisms –  these are molecular processes that commence after the interaction of the drug with the receptor. For example, it is known that hypoglycemia (low blood glucose) in an organism produces a release of catecholamines, which trigger compensation mechanisms thereby increasing blood glucose levels. The release of catecholamines also triggers a series of symptoms, which allows the organism to recognize what is happening and which act as a stimulant for preventative action (eating sugars). Should a patient be taking a drug such as insulin, which reduces glycemia, and also is taking another drug such as certain beta-blockers for heart disease, then the beta-blockers will act to block the adrenaline receptors. This will block the reaction triggered by the catecholamines should a hypoglycemic episode occur. Therefore, the body will not adopt corrective mechanisms and there will be an increased risk of a serious reaction resulting from the ingestion of both drugs at the same time.

  1. Antagonist physiological systems –Imagine a drug A that acts on a certain organ. This effect will increase with increasing concentrations of physiological substance S in the organism. Now imagine a drug B that acts on another organ, which increases the amount of substance S. If both drugs are taken simultaneously it is possible that drug A could cause an adverse reaction in the organism as its effect will be indirectly increased by the action of drug B. An actual example of this interaction is found in the concomitant use of digoxin and furosemide. The former acts on cardiac fibers and its effect is increased if there are low levels of potassium (K) in blood plasma. Furosemide is a diuretic that lowers arterial tension but favors the loss of K+. This could lead to hypokalemia (low levels of potassium in the blood), which could increase the toxicity of digoxin.

Pharmacokinetic interactions

Modifications in the effect of a drug are caused by differences in the absorption, transport, distribution, metabolization or excretion of one or both of the drugs compared with the expected behavior of each drug when taken individually. These changes are basically modifications in the concentration of the drugs. In this respect, two drugs can be homergic if they have the same effect in the organism and heterergic if their effects are different.

Absorption interaction

Changes in motility

Some drugs, such as the prokinetic agents increase the speed with which a substance passes through the intestines. If a drug is present in the digestive tract’s absorption zone for less time its blood concentration will decrease. The opposite will occur with drugs that decrease intestinal motility.

  • pH – Drugs can be present in either ionized or non-ionised form, depending on their pKa (pH at which the drug reaches equilibrium between its ionized and non-ionised form). The non-ionized forms of drugs are usually easier to absorb, because they will not be repelled by the lipidic bilayer of the cell, most of them can be absorbed by passive diffusion, unless they are too big or too polarized (like glucose or vancomycin), in which case they may have or not specific and non specific transporters distributed on the entire intestine internal surface, that carry drugs inside the body. Obviously increasing the absorption of a drug will increase its bioavailability, so, changing the drug’s state between ionized or not, can be useful or not for certain drugs.
  • Drug solubility – The absorption of some drugs can be drastically reduced if they are administered together with food with high fat content. This is the case for oral anticoagulants and avocado.

Formation of non-absorbable complexes

  • Chelation – The presence of di- or trivalent cations can cause the chelation of certain drugs, making them harder to absorb. This interaction frequently occurs between drugs such as tetracycline or the fluoroquinolones and dairy products (due to the presence of Ca++).
  • Binding with proteins –  Some drugs such as sucralfate binds to proteins, especially if they have a high bioavailability. For this reason, its administration is contraindicated in enteral feeding.
  • Another possibility  – is that the drug is retained in the intestinal lumen forming large complexes that impede its absorption. This can occur with cholestyramine if it is associated with sulfamethoxazole, thyroxine, warfarin or digoxin.
  • Acting on the P-glycoprotein of the enterocytes – This appears to be one of the mechanisms promoted by the consumption of grapefruit juice in increasing the bioavailability of various drugs, regardless of its demonstrated inhibitory activity on first pass metabolism.

A drug interaction can be defined as an interaction between a drug and another substance that prevents the drug from performing as expected. This definition applies to interactions of drugs with other drugs (drug-drug interactions), as well as drugs with food (drug-food interactions) and other substances.

Drug interaction
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How do drug interactions occur?

There are several mechanisms by which drugs interact with other drugs, food, and other substances. An interaction can result when there is an increase or decrease in:

  • the absorption of a drug into the body
  • distribution of the drug within the body
  • alterations made to the drug by the body (metabolism) and
  • elimination of the drug from the body.

Most of the important drug interactions result from a change in the absorption, metabolism, or elimination of a drug. Drug interactions also may occur when two drugs that have similar (additive) effects or opposite (canceling) effects on the body are administered together. For example, there may be major sedation when two drugs that have sedation as side effects are given, for example, narcotics and antihistamines. Another source of drug interactions occurs when one drug alters the concentration of a substance that is normally present in the body. The alteration of this substance reduces or enhances the effect of another drug that is being taken. The drug interaction between warfarin (Coumadin) and vitamin K-containing products is a good example of this type of interaction. Warfarin acts by reducing the concentration of the active form of vitamin K in the body. Therefore, when vitamin K is taken, it reduces the effect of warfarin.

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Drug interaction

Change in absorption

Most drugs are absorbed into the blood and then travel to their site of action. Most drug interactions that are due to altered absorption occur in the intestine. There are various potential mechanisms through which the absorption of drugs can be reduced. These mechanisms include:

  1. alteration in blood flow to the intestine;
  2. change in drug metabolism (breakdown) by the intestine;
  3. increased or decreased intestinal motility (movement);
  4. alterations in stomach acidity, and
  5. a change in the bacteria that reside in the intestine.

Drug absorption also can be affected if the drug’s ability to dissolve (solubility) is changed by another drug or if a substance (for example, food) binds to the drug and prevents its absorption.

Change in drug metabolism and elimination

Most drugs are eliminated through the kidney in either an unchanged form or as a by-product that results from the alteration (metabolism) of the drug by the liver. Therefore, the kidney and the liver are very important sites of potential drug interactions. Some drugs are able to reduce or increase the metabolism of other drugs by the liver or their elimination by the kidney.

Metabolism of drugs is the process through which the body converts (alters or modifies) drugs into forms that are more or less active (for example, by converting drugs that are given in inactive forms into their active forms that actually produce the desired effect) or that are easier for the body to eliminate through the kidneys. Most drug metabolism takes place in the liver, but other organs also may play a role (for example, the kidneys, intestine, etc.). The cytochrome P450 enzymes are a group of enzymes in the liver that is responsible for the metabolism of most drugs. They are, therefore, often involved in drug interactions. Drugs and certain types of food may increase or decrease the activity of these enzymes and therefore affect the concentration of drugs that are metabolized by these enzymes. An increase in the activity of these enzymes leads to a decrease in the concentration and effect of an administered drug. Conversely, a decrease in enzyme activity leads to an increase in drug concentration and effect.

Consequences of drug interactions

Drug interactions may lead to an increase or decrease in the beneficial or the adverse effects of the given drugs. When a drug interaction increases the benefit of the administered drugs without increasing side effects, both drugs may be combined to increase the control of the condition that is being treated. For example, drugs that reduce blood pressure by different mechanisms may be combined because the blood pressure lowering effect achieved by both drugs may be better than with either drug alone.

The absorption of some drugs is increased by food. Therefore, these drugs are taken with food in order to increase their concentration in the body and, ultimately, their effect. Conversely, when a drug’s absorption is reduced by food, the drug is taken on an empty stomach.

Drug interactions that are of greatest concern are those that reduce the desired effects or increase the adverse effects of the drugs. Drugs that reduce the absorption or increase the metabolism or elimination of other drugs tend to reduce the effects of other drugs. This may lead to failure of therapy or warrant an increase in the dose of the affected drug. Conversely, drugs that increase absorption or reduce the elimination or metabolism of other drugs – increase the concentration of the other drugs in the body – and lead to increased amounts of the drug in the body and more side effects. Sometimes, drugs interact because they produce similar side effects. Thus, when two drugs that produce similar side effects are combined, the frequency and severity of the side effect are increased.

How often do drug interactions occur?

The prescribing information for most drugs contains a list of potential drug interactions. Many of the listed interactions may be rare, minor, or only occur under specific conditions and may not be important. Drug interactions that cause important changes in the action of a drug are of greatest concern.

Drug interactions are complex and chiefly unpredictable. A known interaction may not occur in every individual. This can be explained because there are several factors that affect the likelihood that a known interaction will occur. These factors include differences among individuals in their:

  • genes,
  • physiology,
  • age,
  • lifestyle (diet, exercise),
  • underlying diseases,
  • drug doses,
  • the duration of combined therapy, and
  • the relative time of administration of the two substances. (Sometimes, interactions can be avoided if two drugs are taken at different times.)
Examples of interactions at the intestinal absorption level: selection of relevant substrates, inducers, and inhibitors of P-glycoprotein (ABCB1)
GroupSubstance
Substrates
  • Opioids
Loperamide, morphine
  • Antihypertensives
Aliskiren, carvedilol
  • Anticoagulants
Dabigatran
  • Cardiac glycosides
Digoxin
  • Immunosuppressants
Ciclosporin, tacrolimus, sirolimus
  • Protease inhibitors
Indinavir, saquinavir
StatinsAtorvastatin, lovastatin, simvastatin
  • Antineoplastic agents
Paclitaxel, anthracyclines, vinca alkaloids, etoposide, imatinib
Inducers
  • Anticonvulsants
Carbamazepine (oxcarbazepine less so), phenytoin, phenobarbital, primidone
  • Tuberculostatics
Rifampicin
  • Antiretroviral
Efavirenz
  • St. John’s wort extract
Hyperforin
Inhibitors
  • Antimycotics
Itraconazole, ketoconazole
  • Calcium channel blockers
Diltiazem; felodipine; nicardipine; nifedipine; verapamil especially
  • Macrolide antibiotics
Erythromycin, clarithromycin, not azithromycin
  • HIV protease inhibitors
Indinavir; nelfinavir; ritonavir especially; saquinavir
  • Immunosuppressants
Ciclosporin
  • Antiarrhythmic drugs
Amiodarone, quinidine, propafenone
Interactions at the cytochrome P450 enzyme level: selection of relevant substrates for which, when used in combination with inhibitors or inducers of the same enzyme, either increased effects and increased occurrence of unwanted effects, or reduced effects or loss of effect must be anticipated (modified from [])
CYP1A2CYP2C9CYP2C19CYP2D6CYP3A4/5
ClozapineNSAIDsProton pumpBeta-blockersMacrolide antibioticsStatins
ImipramineCelecoxibinhibitorsMetoprololClarithromycinAtorvastatin
MexiletineDiclofenacOmeprazolePropafenoneErythromycinLovastatin
NaproxenIbuprofenLansoprazoleTimololSimvastatin
TacrineNaproxenBenzodiazepines
TheophyllinePiroxicamMiscellaneousAntidepressantsAlprazolamAnticoagulants
AmitriptylineAmitriptylineDiazepamApixaban
AntidiabeticsClomipramineClomipramineMidazolamRivaroxaban
GlipizideClopidogrel*DesipramineTriazolamPhenprocoumon
TolbutamideCyclophosphamide*Duloxetine
DiazepamImipramineCalcium channelMiscellaneous
Angiotensin receptorPhenytoinParoxetineblockersAripiprazole
blockersVenlafaxineAmlodipineBuspirone
IrbesartanDiltiazemQuinidine
LosartanAntipsychoticsFelodipineQuinine
AripiprazoleNifedipineEthinylestradiol
MiscellaneousHaloperidolNisoldipineImatinib
CyclophosphamideRisperidoneNitrendipineSildenafil
FluvastatinThioridazineVerapamilTamoxifen
PhenytoinVincristine
SulfamethoxazoleOpioidsImmunosuppressants
TorasemideCodeine*Ciclosporin
WarfarinDextromethorphanTacrolimus
Tramadol*Sirolimus
MiscellaneousHIV protease inhibitors
OndansetronIndinavir
Tamoxifen*Ritonavir
Saquinavir

Overview of selected serious drug interactions[]

InteractionPotential effectTime to effectRecommendations and comments
  • Warfarin (Coumadin)  plus ciprofloxacin (Cipro), clarithromycin (Biaxin), erythromycin, metronidazole (Flagyl) or trimethoprim-sulfamethoxazole (Bactrim, Septra)
Increased effect of warfarinGenerally within 1 weekSelect alternative antibiotic
  • Warfarin  plus acetaminophen
Increased bleeding, increased INRAny timeUse lowest possible acetaminophen dosage and monitor INR
  • Warfarin plus acetylsalicylic acid (aspirin)
Increased bleeding, increased INRAny timeLimit aspirin dosage to 100 mg per day and monitor INR
  • Warfarin  plus NSAID
Increased bleeding, increased INRAny timeAvoid concomitant use if possible; if coadministration is necessary, use a cyclooxygenase-2 inhibitor and monitor INR
  • Fluoroquinolone  plus divalent/trivalent cations or sucralfate (Carafate)
Decreased absorption of fluoroquinoloneAny timeSpace administration by 2–4 h
  • Carbamazepine (Tegretol)  plus cimetidine (Tagamet), erythromycin, clarithromycin or fluconazole (Diflucan)
Increased carbamazepine levelsGenerally within 1 weekMonitor carbamazepine levels
  • Phenytoin (Dilantin) plus cimetidine, erythromycin, clarithromycin or fluconazole
Increased phenytoin levelsGenerally within 1 weekMonitor phenytoin levels
  • Phenobarbital  plus cimetidine, erythromycin, clarithromycin or fluconazole
Increased phenobarbital levelsGenerally within 1 weekClinical significance has not been established.
Monitor phenobarbital levels
  • Phenytoin plus rifampin (Rifadin)
Decreased phenytoin levelsGenerally within 1 weekClinical significance has not been established.
Monitor phenytoin levels
  • Phenobarbital plus rifampin
Decreased phenobarbital levelsGenerally within 1 weekMonitor phenobarbital levels
  • Carbamazepine plus rifampin
Decreased carbamazepine levelsGenerally within 1 weekClinical significance has not been established. Monitor carbamazepine levels
  • Lithium plus NSAID or diuretic
Increased lithium levelsAny timeDecrease lithium dosage by 50% and monitor lithium levels
  • Oral contraceptive pills plus rifampin
Decreased effectiveness of oral contraceptionAny timeAvoid if possible. If combination therapy is necessary, have the patient take an oral contraceptive pill with a higher estrogen content (>35 µg of ethinyl estradiol) or recommend alternative method of contraception
  • Oral contraceptive pills plus antibiotics
Decreased effectiveness of oral contraceptionAny timeAvoid if possible. If combination therapy is necessary, recommend use of alternative contraceptive method during cycle
  • Oral contraceptive pills plus troglitazone (Rezulin)
Decreased effectiveness of oral contraceptionAny timeHave the patient take an oral contraceptive pill with a higher estrogen content or recommend an alternative method of contraception
  • Cisapride (Propulsid) plus erythromycin, clarithromycin, fluconazole, itraconazole (Sporanox), ketoconazole (Nizoral), nefazodone (Serzone), indinavir (Crixivan) or ritonavir (Norvir)
Prolongation of QT interval along with arrhythmias secondary to inhibited cisapride metabolismGenerally within 1 weekAvoid. Consider whether metoclopramide (Reglan) therapy is appropriate for the patient
  • Cisapride plus class IA or class III antiarrhythmic agents, tricyclic antidepressants or phenothiazine
Prolongation of QT interval along with arrhythmiasAny timeAvoid. Consider whether metoclopramide therapy is appropriate for the patient
Dramatic hypotensionSoon after taking sildenafilAbsolute contraindication
  • Sildenafil plus cimetidine, erythromycin, itraconazole or ketoconazole
Increased sildenafil levelsAny timeInitiate sildenafil at a 25-mg dose
  • HMG-CoA reductase inhibitor plus niacin, gemfibrozil (Lopid), erythromycin or itraconazole
Possible rhabdomyolysisAny timeAvoid if possible. If combination therapy is necessary, monitor the patient for toxicity
  • Lovastatin (Mevacor) plus warfarin
Increased effect of warfarinAny timeMonitor INR
  • SSRI plus tricyclic antidepressant
Increased tricyclic antidepressant levelAny timeMonitor for anticholinergic excess and consider lower dosage of tricyclic antidepressant
  • SSRI  plus selegiline (Eldepryl) or nonselective monoamine oxidase inhibitor
Hypertensive crisisSoon after initiationAvoid
  • SSRI plus tramadol (Ultram)
Increased potential for seizures; serotonin syndromeAny timeMonitor the patient for signs and symptoms of serotonin syndrome
  • SSRI plus St. John’s wort
Serotonin syndromeAny timeAvoid
  • SSRI plus naratriptan (Amerge), rizatriptan (Mazalt), sumatriptan (Imitrex) or zolmitriptan (Zomig)
Serotonin syndromePossibly after initial doseAvoid if possible. If combination therapy is necessary, monitor the patient for signs and symptoms of serotonin syndrome
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INR, International Normalized Ratio; NSAID, nonsteroidal anti-inflammatory drug; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor; SSRI, selective serotonin reuptake inhibitor

Ways to Prevent a Deadly Drug Interaction

  • You should not be afraid to take your medications because of the possibility of drug interactions. Drug interactions can be intimidating for anyone who regularly takes prescription medications, but you can learn how to manage and prevent them.
  • Nevertheless, important drug interactions occur frequently and they add millions of dollars to the cost of health care. Moreover, many drugs have been withdrawn from the market because of their potential to interact with other drugs and cause serious health care problems.
  • Drugs with a narrow therapeutic index (that is, having little difference between toxic and therapeutic doses), and certain disease states like epilepsy or depression are especially prone to serious drug interactions. In addition, multiple interactions may occur when someone is taking several drugs, as is often the case with older patients.
  • While most interactions are usually not life-threatening, some mixtures of medications can lead to serious — and even fatal — consequences. Pharmacists and doctors are well-trained to review and predict drug interactions. You can also use online drug interactions tools to help gauge the risk prior to discussing with your doctor or pharmacist.
  • Education and communication are key. You should consult with your health care providers, research reliable drug information, and empower yourself to lower the risk of interactions and maximize your medical treatments. Here are nine tips to achieve that goal.

Management of Drug Interaction

The role of pharmacogenetics and pharmacogenomics[]

  • An individual’s genetic makeup can alter their response to a drug. Genetics affect pharmacokinetics and pharmacodynamics. Unrecognized mutations can be associated with ADRs or can affect the magnitude of a drug interaction. A common example is the metabolism of ethanol. There are ethnic differences in the metabolism of ethanol by alcohol dehydrogenase. People of Chinese descent have a higher incidence of atypical alcohol dehydrogenase and therefore become flushed and dizzy when they consume alcohol. Their capacity for consuming alcohol is lower than that for other populations.
  • To apply pharmacogenetics and pharmacogenomics to the management of drug interactions, it is important to know the difference between the two terms. Pharmacogenetics applies to inherited traits and genetic polymorphisms. Polymorphism refers to stable allelic variations found in the population (occurring at a frequency >1%) that result in altered protein activity. Pharmacogenomics applies to the entire spectrum of genes. With pharmacogenetics, the focus is on metabolizing enzymes and transporters, whereas with pharmacogenomics, the focus is on individualized drug and dosage for a specific disease.

The role of the pharmacist in the management of drug interaction

  • The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. The practice in clinical pharmacy also ensures that ADRs are minimized by avoiding drugs with potential side effects in susceptible patients. Thus, the pharmacist has a major role to play in relation to prevention, detection, and reporting ADRs.[]

Management options of drug interaction include

  • Avoiding the combination entirely – For some drug interactions, the risk always outweighs the risk, and the combination should be avoided. Because drug classes are usually heterogeneous with regard to drug interactions (as described above), one can often select a no interacting alternative for either the object drug or the precipitant drug.[]
  • Adjusting the dose of the object drug Sometimes, it is possible to give the two interacting drugs safely as long as the dose of the object drug is adjusted.
  • Spacing dosing times to avoid the interaction  For some drug interactions involving binding in the gastrointestinal tract, to avoid the interaction one can give the object drug at least 2 h before or 4 h after the precipitant drug. In this way, the object drug can be absorbed into the circulation before the precipitant drug appears.
  • Monitoring for early detection  In some cases, when it is necessary to administer interacting drug combinations, the interaction can be managed through close laboratory or clinical monitoring for the evidence of the interaction. In this way, the appropriate dosage changes can be made, or the drugs discontinued if necessary.
  • Provide information on patient risk factors that increase the chance of an adverse outcome –  It is clear from the clinical experience of physicians and pharmacists as well as published studies that most patients who take interacting drug combinations do not manifest adverse consequences.[] Substantial evidence from both the clinical experience of physicians and pharmacists as well as published studies suggest that the risk of statin-induced myopathy increases with increasing serum concentrations of the statin. Accordingly, it has been recommended that simvastatin should not exceed 20 mg daily in patients receiving verapamil concurrently.[]
  • Improve computerized screening systems  It is clear that computerized drug interaction screening systems have not been as successful as one hoped.[,]
  • The excessive number of drug interactions on the systems – Many pharmacists find that computerized drug interaction screening systems detect a large number of DDIs of questionable clinical significance.
  • Drug class differences not handled correctly  Almost all drug classes interact heterogeneously because individual members of a drug class are often not metabolized by the same cytochrome P450 isozymes or ABC (ATP-binding cassette) transporters as other members of the class. The statins are a good example, because simvastatin and lovastatin are extensively metabolized by CYP3A4, atorvastatin is moderately metabolized by CYP3A4, fluvastatin is metabolized by CYP2C9, and pravastatin and rosuvastatin are not metabolized by cytochrome P450 isozymes.[] Thus, combining all members of this drug class together is rarely justified when considering drug interactions. Nonetheless, it is common for reviews and computer systems to include all statins together as interacting with CYP3A4 inhibitors, even though the risk is primarily limited to lovastatin, simvastatin, and to a lesser extent, atorvastatin.[]

Management[]

  • Before starting any new prescription drug or over-the-counter drug, talk to your primary health care provider or pharmacist. Make sure that they are aware of any vitamins or supplements that you take.
  • Make sure to read the patient information handout given to you at the pharmacy. If you are not given an information sheet, ask your pharmacist for one.
  • Check the labels of your medications for any warnings and look for the “Drug Interaction Precaution.” Read these warnings carefully.
  • Make a list of all your prescription medications and over-the-counter products, including drugs, vitamins, and supplements. Review this list with all health care providers and your pharmacist.
  • If possible, use one pharmacy for all your prescription medications and over-the-counter products. This way your pharmacist has a record of all your prescription drugs and can advise you about drug interactions and side effects.

This brief overview of drug interactions does not cover every possible scenario. Individuals should not be afraid to use their drugs because of the potential for drug interactions. Rather, they should use the information that is available to them to minimize the risk of such interactions and to improve the success of their therapy.[,]

Some Community Guideline for Pharmacist

Performing or obtaining necessary assessments of the patient’s health status is as follows

  • Formulating a medication treatment plan: selecting, initiating, modifying, or administering medication therapy.
  • Monitoring and evaluating the patient’s response to therapy, including safety and effectiveness.
  • Performing a comprehensive medication review to identify, resolve, and prevent medication-related problems, including adverse drug events.
  • Documenting the care delivered and communicating essential information to the patient’s other primary care providers.
  • Providing verbal education and training designed to enhance patient understanding and appropriate use of his or her medications.
  • Providing information, support services, and resources designed to enhance patient adherence with his or her therapy.
  • Coordinating and integrating medication therapy management services within the broader health care management services being provided to the patient.
  • Give health care practitioners a complete list of all of the drugs that you are using or have used within the last few weeks. This should include over-the-counter medications, vitamins, food supplements, and herbal remedies.
  • Inform health care practitioners when medications are added or discontinued.
  • Inform health care practitioners about changes in lifestyle (for example, exercise, diet, alcohol intake).
  • Ask your health care practitioners about the most serious or frequent drug interactions with the medications that you are taking.
  • Since the frequency of drug interactions increases with the number of medications, work with your health care practitioners to eliminate unnecessary medications.

Communicate Frequently

Tell your pharmacist each time you start or stop a medication, including any over-the-counter (OTC) drug, herbal supplement, or vitamin. Keep an updated list of meds, including nonprescription drugs — and share with your health care providers, including your dentist, anytime you start or stop a medication.

  • Prescription drugs are not the only medicines that can interact. Non-prescription drugs can have serious consequences, too. For example, the herbal St. John’s Wort is commonly used as an OTC supplement for depression. If combined with other antidepressants such as the SSRIs like fluoxetine (Prozac) or sertraline (Zoloft), the risk of a rare but serious and potentially fatal condition called serotonin syndrome can occur, with symptoms such as confusion, hallucination, seizure, extreme changes in blood pressure, and even death.
  • Read your Medication Guide each time you get a new prescription or refill. The FDA updates prescription drug labels frequently, and there could be changes in your Medication Guide. Review your possible interactions and ask questions if you are concerned or don’t quite understand the medical jargon.
  • If you discover that you are at risk for an interaction, call your doctor. It may be that the interaction is minor, and no action is needed. On the other hand, you may need to avoid the drug or have an alternative medicine prescribed. NEVER stop a medication without first speaking to your doctor.
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Research Your Meds Yourself

  • Use a reliable online drug interaction tool like the Drugs.com Interaction Checker to become engaged in your health and learn about your medications. If you need help understanding the information, be sure to call your pharmacist. Always check for drug interactions even when you purchase OTC medications, herbal supplements or vitamins.
  • The Drug Interaction Checker explains the mechanism of each drug interaction, the level of significance of the interaction (major, moderate or minor), and in certain cases, can provide the recommended course of action to manage the interaction. The Drug Interaction Checker will also display any interactions between your chosen drug(s), food or beverages, and even other diseases.
  • To see all possible drug interactions, just enter one drug name and select “check for interactions.” Information is provided for all interactions at both the consumer and professional level.

Keep All of Your Prescriptions at One Pharmacy

  • By keeping all of your prescriptions at one pharmacy, a regular drug review and drug interaction screen can be done electronically that incorporates all of your medicines. Talk with your pharmacist and doctor and communicate new and discontinued medications with all of your health care providers. Communication is key to preventing drug interactions.
  • When you buy OTCs or herbal supplements, ask your pharmacist to double check for interactions and ask if they can add the agent to your regular drug profile for future drug interaction checks. If your pharmacist does not know that you are taking OTC products, they can’t check for drug interactions with prescription medication. Be sure to read the Drug Facts Label on each OTC product you use, too.

Take Any Food and Beverage Drug Interactions Seriously

  • Your pharmacist or doctor may ask about specific foods or drinks you consume depending upon which drugs you take. Common food items involved in drug interactions include foods rich in vitamin K, which can interact with certain blood thinners like warfarin and make them less effective, possibly leading to a clot. Certain citrus juices like grapefruit juice are notorious for changing blood levels of some drugs, too. Calcium can bind with some drugs and prevent absorption.
  • For example, if you take the blood thinner warfarin, increasing vitamin K levels in the body can increase clotting and reduce the effectiveness of warfarin, which could result in a stroke. Foods rich in vitamin K include beef liver, broccoli, brussels sprouts, cabbage, collard greens, endive, kale, lettuce, mustard greens, parsley, soy beans, spinach, Swiss chard, turnip greens, watercress, and several other foods. While there is no need to avoid products that contain vitamin K, you should maintain a consistent level of consumption of these products.
  • Grapefruit or grapefruit juice consumption can also result in drug interactions that may increase the level of the medicine in your blood, possibly causing drug toxicity. For example, blood levels of some cholesterol drugs known as statins —  atorvastatin, lovastatin, or simvastatin —  can be affected by drinking grapefruit juice, and lead to severe muscle injury known as rhabdomyolysis. Not all medicines contained in a class of drugs like the statins may lead to the interaction, so your doctor will be able to prescribe another drug. Cranberry juice, orange juice, pomegranate juice, and even garlic can lead to interactions with drugs, too.

Tell Your Doc About Caffeine Use, Alcohol Use, and Illegal Drug Use

  • Socially-used drugs can have an especially harsh effect with other drugs. For example, some asthma drugs like the beta-2 agonist albuterol (Proventil HFA, Ventolin HFA) can have a stimulant effect, and if combined with caffeine, can interfere with sleep or lead to a rapid heart rate, which can be dangerous in people woth heart disease. The stimulant effect from caffeine can be additive to stimulation from decongestants, too.
  • Alcohol can worsen drowsiness, especially when mixed with other drugs that cause sedation, which may put you at a higher risk for a fall or a car accident. Alcohol should never be combined with opioid painkillers or anxiety medications like benzodiazepines. Life-threatening respiratory depression can occur.
  • A particularly concerning, yet often unknown interaction between alcohol and cocaine has been reported. The National Institute on Drug Abuse (NIDA) has found that the human liver combines cocaine and alcohol and manufactures a third substance, cocaethylene, that intensifies cocaine’s euphoric effects but may increase the risk of sudden death. According to the NIDA, this drug-drug interaction, between cocaine and alcohol, is the most common two-drug combination that results in drug-related deaths.
  • Illicit drugs combined with other illicit drugs can be particularly dangerous. Combining heroin and cocaine into one syringe, often called a “speedball”, is a mixture that is used by some injecting drug users, often with fatal results.

Don’t Take a Medication Prescribed for Someone Else

  • Medications are prescribed specifically for an individual person, often based on their age, weight, and specific type of medical condition. In addition, when you take medications that are not prescribed for you, there is no health care provider involved to review for potential interactions or safety based on your medical conditions.
  • For example, taking someone else’s antibiotic for a sore throat might not only lead to a possible drug interaction, it might worsen your infection. The antibiotic might not be the appropriate drug to treat the bacterial strain, and you probably won’t have a full course of antibiotic which can result in antibiotic resistance and failed treatment. Plus, if your sore throat is viral, instead of bacterial, you may not need an antibiotic at all. Your doctor can test you for this.

Follow All Dosing Recommendations on Your Prescription Bottle

  • Your prescription bottle will have specific directions for taking your medicine. For example, you may need to space the timing of when you take your medications. Some drug interactions involve binding of one drug to the other in the stomach. Antacids are commonly linked to this type of interaction. Your pharmacist will put a sticker on the your bottle to warn you of this interaction. To avoid the interaction you may space the timing of your doses, taking each drug 2 hours before or 4 hours after the other drug.
  • Antacids can also raise the pH in your stomach, and may result in an early dissolution of enteric coatings — for example, enteric-coated aspirin or ibuprofen — which should normally dissolve in the intestine. This could lead to severe stomach bleeding or lowered absorption of the drug. Your pharmacist will provide specific instructions.
  • DO NOT change the dose of your medication unless approved by your doctor. If your warning sticker suggests that you avoid a drug, or a certain class of drugs altogether, be sure to follow these instructions. Many patients that take blood thinners like warfarin need to avoid over-the-counter and prescription drugs that may increase the risk of bleeding; for example, NSAIDs (ibuprofen, naproxen) or aspirin.

Tell Your Health Care Provider About Your Medical Conditions

  • In people who have high blood pressure, OTC oral decongestants like pseudoephedrine (Sudafed) or phenylephrine (Sudafed PE) may increase blood pressure, even if their blood pressure is controlled with a medication. People with uncontrolled or severe high blood pressure need to avoid these medications.
  • Another common example of a disease-drug interaction is the use of the antihistamine diphenhydramine (Benadryl) in patients with certain types of glaucoma known as acute angle-closure (narrow-angle) glaucoma. For example, diphenhydramine can exhibit anticholinergic effects which can dilate the pupil and provoke angle closure in people with narrow angles. Antihistamines should be avoided in people with angle-closure glaucoma or only used under the supervision of a physician.

Do NOT Buy Drugs From Risky Online Pharmacies

  • While it may be a tempting way to save money on medications, buying medications — prescription or OTC — from foreign countries or from unreliable websites on the Internet can be costly to your health. According to the U.S. Food and Drug Administration “the safety and effectiveness of imported drugs have not been reviewed by the FDA, and their identity and potency can’t be assured.” You could receive the wrong drug, the wrong strength, or even outdated, expired medications. If you are not sure what’s in your medication, you can’t run a reliable drug interaction check to look for any serious problems.

How can drug interactions be avoided

  • Give health care practitioners a complete list of all of the drugs that you are using or have used within the last few weeks. This should include over-the-counter medications, vitamins, food supplements, and herbal remedies.
  • Inform health care practitioners when medications are added or discontinued.
  • Inform health care practitioners about changes in lifestyle (for example, exercise, diet, alcohol
  • intake).
  • Ask your health care practitioners about the most serious or frequent drug interactions with the medications that you are taking.
  • Since the frequency of drug interactions increases with the number of medications, work with your health care practitioners to eliminate unnecessary medications.

References

Drug interaction

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3 thoughts on “Drug Interaction; Types, Prevention, Complication”

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