eMedExpert Home > Safe Medication Use

To make medication use as much safe and effective as possible:

• Ask questions
• Speak up
• Educate yourself
• Evaluate your choices
• Find the facts
• Read the label and follow directions

1List all medications you take. Keep up-to date list of all the medications you take in a wallet or purse. Include name, dose and frequency. Don't forget to include vitamin and mineral supplements; herbal remedies; skin, rectal or vaginal medications; eyedrops and eardrops; inhalants and nasal sprays; weight loss aids; oral contraceptives. Update it after every doctor visit. Periodically discuss this list with the doctor or pharmacist.

2Medical history. Make sure that all of your doctors, your dentist and your pharmacist know your medical history, including any allergies, illness, previous bad drug experience.

3Future medical plans. Discuss with your doctor plans to elective surgery (including dental surgery), pregnancy and breast feeding. These conditions may require discontinuing or modifying the dosages of medications.

4Question anything you don't understand or that doesn't seem right. Don’t hesitate to ask questions or express your concerns. If you are unsure you are using your medication correctly, or are unclear about its effects or purpose, ask your pharmacist or doctor.

Recent observational studies of medication errors in community pharmacies suggest that "wrong drug" errors, which occur when a patient receives a drug other than the one prescribed, may occur as many as 3.9 million times per year in the US. Similarity between drug names, is thought to be a contributing cause of these errors[2].

5Know the brand and generic names of the medication. Read the drug name on the label and be sure that you take correct medication. In fact, the average person knows the medication he or she takes by its colour and size rather than its chemical name.

6Know what the medication is for. One of the best ways to avoid mistakes is to learn as much as you can about your medications. It’s important to understand your medication because you are more likely to use it correctly, more likely to know what to expect from the medication, and better able to report what you are using and problems to your doctors and pharmacist.

7Analyze your prescription paper at the doctor's office. Doctors are only human, and they make human mistakes. They may mistakenly write down the wrong medication on their prescription pad, or the wrong dose or frequency.

8Avoid getting the wrong prescription from the pharmacy. Pharmacies can make mistakes. Check the medication you pick up. Make sure the medication matches up with the prescription.

9If you are picking up a refill, compare the pills in the new bottle to any remaining in the previous bottle. The new and old pills should be identical. Be especially alert to unexpected changes, such as receiving a prescription refill that seems to have a different strength or appearance from your original prescription. If the medication is different, ask pharmacist why. It might be as simple as the health plan changed manufacturers, or medication has changed from brand name to generic, he says, but check to be sure.

Overdose toxicity is a serious, often harmful, and sometimes fatal toxic reactions to an accidental overdose of the drug.

10Know the phone number of your regional Poison Control Center. The American Association of Poison Control Centers (AAPCC) uses a single, nationwide emergency number to automatically link callers with their regional poison center. This toll-free number, 800-222-1222, also works for teletype lines (TTY) for hearing-impaired and telecommunication devices (TTD) for individuals who are deaf. However, a few local poison centers and the ASPCA/Animal Poison Control Center are not part of this nationwide system and continue to use separate numbers.

11Know about narrow therapeutic index drugs. Some drugs are identified as having a narrow therapeutic index (NTI) by the FDA. The medication is identified as having a narrow therapeutic index if very small changes in the dosage level could cause either subtherapeutic or toxic results. NTI drugs are identified in the Wellmark Drug List. These medications can be easily overdosed.

Some drugs with narrow therapeutic index include:

• Aminoglycoside antibiotics (amikacin, gentamicin, tobramycin)
• Anticoagulants (warfarin, heparins)
• Aspirin
• Carbamazepine
• Conjugated estrogens
• Cyclosporine
• Digoxin
• Esterified estrogens
• Hypoglycemic agents
• Levothyroxine sodium
• Lidocaine
• Lithium
• monoamine oxidase (MAO)
• Phenobarbital
• Phenytoin
• Primidone
• Procainamide
• Quinidine sulfate/gluconate
• Tacrolimus
• Theophylline
• Tricyclic antidepressants
• Valproic acid
• Vancomycin

12Drugs that may be fatal in overdose:

• Antidepressants (dothiepin, amitriptyline, imipramine, doxepin, clomipramine, trazodone, venlafaxine, tranylcypromine, phenelzine, moclobemide, lithium) [18]
• Colchicine [20]
• Co-trimoxazole, clindamycin, trovafloxacin
• Paracetamol (Acetaminophen) [21], [22]
• Verapamil

A drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug in the body. Avoidance of drug interactions does not necessarily mean avoiding drugs or foods.

Pharmacokinetic interactions influence the disposition of a drug in the body and involve the effects of one drug on the absorption, distribution, metabolism and/or excretion of another drug. These interactions frequently cause marked shifts in serum drug levels and alter clinical response.

Pharmacodynamic interactions are related to the pharmacologic activity of the interacting drugs. These interactions are frequently associated with synergism, antagonism, or altered cellular transport, and they affect organ systems and/or receptor sites.

Knowing about every drug interaction is impractical, and not all drug interactions have adverse clinical consequences.

13Use online drug interaction checker. Use online tools available, that allow you to enter the medications you take and check for possible drug interactions, e.g. http://www.drugs.com/drug_interactions.html

14Ask your doctor to check the list for potential bad interactions when getting a new prescription or samples of a new drug. When you receive a new prescription, remind your doctor of all prescription medications, OTC drugs, supplements and vitamins you're taking. Also, remind your doctor of any allergies.

15Ask your pharmacist for the package insert for each prescription drug you take. The package insert provides more information about potential drug interactions.

16Select a pharmacist who provides comprehensive services (including checking for possible interactions) and who maintains a complete drug profile for each patient, and have all prescriptions dispensed by this pharmacist.

17Be aware about patient risk factors for drug interactions. Conditions that place person at higher risk for drug interactions include:

• Taking three or more medications for chronic conditions. Studies show that the rate of adverse drug reactions increases exponentially in patients taking 4 or more medications [5].
• Genetically based variations in drug-metabolizing capacity. This explains why a medication works well in some individuals but is a treatment failure in others. And some people are "slow metabolizers" or have less active enzymes, while others totally lack specific P450 enzymes. A recent analysis suggests that depending on the drug studied, 60-90% of person-to-person variability in CYP3A function is caused by genetic factors [25], [27].
• Advanced age (age-related changes like diminished metabolism, excretion, and enzyme induction; multiple drugs).
• Certain diseases (aplastic anemia, asthma, cardiovascular disease, critical care/intensive care patients, diabetes, epilepsy, gastrointestinal disease, hepatic (liver) disease, hypothyroid) [29-32].
• Comorbid substance abuse.
• Cigarette smoking (can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms) [28].
• People cared for by several doctors are at higher risk of drug-drug interactions because each doctor may not know all of the drugs being taken.

18Know about drug-related factors. Some drugs likely to be involved in clinically significant interactions [3]:

• Drugs with a narrow therapeutic index (e.g. warfarin, digoxin, antiepileptics, theophylline, cyclosporin)
• Drugs which require careful dosage control (e.g. antihypertensives, antidiabetic drugs)
• Liver enzyme inducers (e.g. rifampicin, phenytoin, carbamazepine, barbiturates) and inhibitors (e.g. cimetidine, ketoconazole, ciprofloxacin, erythromycin)
• Drugs with multiplicity of pharmacological actions

19Be aware about most common Clinically significant drug interactions involving commonly prescribed medications. Although most drug interactions are clinically insignificant, some pose a significant risk. A knowledge of the main types of drugs that are more likely to be involved will act as a useful alert.

• Acetaminophen plus carbamazepine, phenytoin - increased the production of toxic acetaminophen metabolites.
• ACE inhibitors plus potassium-sparing diuretic (spironolactone, amiloride, triamterene), potassium supplements, tacrolimus, cyclosporine - risk of hyperkalemia, a potential cardiac emergency [34].
• Benzodiazepines plus azole antifungals, selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics - increased benzodiazepine effect [36-38].
• Digoxin plus calcium channel blockers, amiodarone, quinidine, azole antifungals, certain antibiotics (tetracyclines, erythromycin, clarithromycin), cyclosporine - increased digoxin toxicity, potentially fatal cardiac arrhythmias [39-46].
• Carbamazepine plus azole antifungals, calcium channel blockers, cimetidine, erythromycin, clarithromycin, metronidazole, valproic acid, sulphonamides - increased risk of carbamazepine toxicity [47-51].
• Fluoroquinolone plus divalent/trivalent cations (aluminum- or magnesium-containing antacids, sucralfate, products containing calcium, iron, or zinc) - marked reduction of absorption of the fluoroquinolone. Studies have shown that the absorption of fluoroqinolones is reduced by 60 to 75 percent when these antibiotics are administered concomitantly with divalent or trivalent cations [52], [53].
• Lithium plus NSAID, diuretic - increased lithium levels. Diuretics and NSAIDs alter the sodium balance at the level of the kidney. As a result, serum lithium levels increase secondary to enhanced reabsorption [54].
• MAO inhibitors plus carbamazepine, tricyclic antidepressants, SSRIs - serotonin syndrome, CNS overstimulation, hyperpyrexia, seizures, and even death [55].
• Oral contraceptive plus rifampin, carbamazepine, phenobarbital, phenytoin, troglitazone - decreased effectiveness of oral contraception. These agents can reduce the plasma concentrations of oral contraceptives through an P450 isoenzyme-inducing mechanism. The problems are most likely to occur with formulations containing a low dosage of estrogen (less than 35 mg of ethinyl estradiol) [47], [56], [57].
• Phenytoin plus amiodarone, cimetidine, diltiazem, verapamil, isoniazid, metronidazole, erythromycin, clarithromycin, sulfonamides, fluoxetine - increased risk of phenytoin toxicity [50], [58-60].
• Phenytoin plus carbamazepine, doxorubicin, estrogens, oral contraceptives, phenobarbital, rifampin - decreased phenytoin levels and effect.
• Phenobarbital plus cimetidine, erythromycin, clarithromycin, sulphonamides, fluconazole - increased phenobarbital levels [60].
• Quinidine plus tricyclic antidepressants, codeine - increased level of antidepressants or codeine [41].
• Quinidine plus cimetidine, azole antifungals and calcium antagonists - increased quinidine effect [41].
• Sildenafil plus nitrates - risk of severe hypotension, which may lead to cardiovascular collapse. Sildenafil therapy is absolutely contraindicated in patients who are taking any form of nitrates [61].
• Statins (HMG-CoA reductase inhibitors) plus niacin, gemfibrozil, erythromycin, cyclosporine - can cause toxicity that manifests as elevated serum transaminase levels, myopathy, rhabdomyolysis and acute renal failure [62].
• Theophylline plus ciprofloxacin, enoxacin, pefloxacin, ofloxacin, erythromycin, clarithromycin, amiodarone, itraconazole, ketoconazole, fluconazole, cimetidine, quinidine, fluoxetine - theophylline levels can increase to a toxic degree [41], [52], [53], [63-65].
• Triazole antifungals (ketoconazole, fluconazole, and itraconazole) plus phenytoin, warfarin, sulfamethoxazole, cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine, astemizole, losartan - antifungal drugs can cause many clinically significant interactions by increasing the concentrations of other drugs [66].
• Drug interactions involving warfarin are among the most serious, because they are associated with a high risk of fatal bleeding.
  Warfarin plus antibiotic (ciprofloxacin, clarithromycin, erythromycin, metronidazole, trimethoprim-sulfamethoxazole) - Increased effects of warfarin, with potential for bleeding. Reduction of intestinal flora responsible for vitamin K production by antibiotics is probable as well as decreased metabolism and clearance of warfarin [67-70].
• Warfarin plus itraconazole, ketoconazole, fluconazole, cimetidine, omeprazole, amiodarone, propafenone, quinidine, nefazodone, fluoxetine - increased warfarin effect [35], [41], [71-73].
• Warfarin plus acetaminophen, aspirin, NSAIDs - potential for serious gastrointestinal bleeding [72], [74], [75].
• Warfarin plus phenytoin, carbamazepine, phenobarbital, rifampin - decreased warfarin effect [76].

20Common interactions with over-the-counter medications (some of the worst/most dangerous drug-drug interactions involving over-the-counter medications):

• Aspirin can significantly increase the effect of blood thinning drugs (anticoagulants), thus increasing the risk of excessive bleeding.
• Antacids can cause anticoagulants to be absorbed too slowly.
• Antacids can interfere with drug absorption of antibiotics (e.g. tetracyclines, fluoroquinolones), thereby reducing the effectiveness of the drug in fighting infection.
• Antihistamines, often used for allergies and colds, can increase the sedative effects of barbiturates, tranquilizers, and some prescription pain relievers.
• Decongestants in cold and cough medications can interact with antihypertensive medications and aggravate high blood pressure [33].
• Iron supplements taken with antibiotics can reduce or stop the ability of the antibiotics to fight infection.
• Salt substitutes can interact with "water" pills or blood pressure medication to increase blood potassium levels. This can result in symptoms of nausea, vomiting, muscle cramp diarrhea, muscle weakness, and cardiac arrest.

Adverse drug reactions are one of the leading causes of death in the United States.

An adverse drug reaction (ADR) can be defined as an unexpected diminished or enhanced pharmacologic activity or toxicity of a drug when used alone, or any noxious response to a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. A drug’s failure to achieve its intended effect is not considered an ADR. This definition also includes any undesirable or unexpected event requiring discontinuation of the drug, modification of the dose, prolonged hospitalization, or the administration of supportive treatment.

21Know what to expect from your medication:

• How soon you should notice an improvement (onset of drug action)?
• What are possible side effects?
• Will the medicine take the place of any other medicine you have been using?
• Is there any chance that you could become tolerant, dependent or addicted to the medication? What can you do to avoid this?

22Report doctor about any problems that you develop after starting a new drug. Pay attention to how you feel after starting the new medicine and note any changes. Assume that any new symptom you develop after starting a new medication might be caused by the drug. A change in the dose or a change in medicine may be needed.

23When adding a new drug, check if it is possible to discontinue another drug.

24Use newly FDA approved medications with caution. FDA approval process does not guarantee protection from serious adverse events. The safety of new agents cannot be known with certainty until a drug has been on the market for many years. Half of the black-box warning changes occurre within 7 years of drug introduction. Half of the withdrawals occurre within 2 years.

25Off-label drug use is associated with increased risk of adverse drug reactions. Off-label drug use means prescribing a drug for a condition for which it has not received FDA approval. The term also refers to drugs ordered for a different population group, such as children instead of adults, or at a different dose or duration than was determined by the FDA to have a favorable risk-benefit ratio. Throughout the world, many drugs prescribed for children are used in an off-label or unlicensed manner. The risk associated with unlicensed and off-label drug use appears to be greater than for prescribing in accordance with the product licence [78].

26Make sure your doctor knows about any allergies and adverse reactions you have had to medicines. Some medications have cross-reactivity. For example, almost one third of penicillin-allergic children are sensitized to cephalosporins (cross-reactivity between cephalosporins and penicillins) [103].

27Know about risk factors for hypersensitivity reactions (interactions between a pharmacologic agent and the human immune system). Risk factors for drug hypersensitivity reactions include age, female gender, concurrent illnesses, and previous hypersensitivity to related drugs. Another factor is the route of drug administration. Topical, intramuscular, and intravenous administrations are more likely to cause hypersensitivity reactions. Oral medications are less likely to result in drug hypersensitivity [77].

28Avoid treating adverse drug reactions and drug-induced disease with more drugs. Distinguish the real disease and adverse reaction to the medication. Adverse drug reaction should be managed by lowering the dose of the offending drug or replacing it with a safer alternative. Adding a second drug to “treat” the adverse drug reaction caused by the first drug can lead to further problems. Common drug-induced conditions include: parkinsonism, depression, sexual dysfunction, insomnia, psychoses, constipation.

Some examples of the treatment of adverse drug reactions with more drugs:

• Antihypertensive agents are frequently prescribed for patients whose high blood pressure is a result of NSAID use.
• Gout medications are initiated to treat mild hyperuricemia from thiazide diuretics.
• Parkinsonian symptoms resulting from metoclopramide are over-treated with levodopa.

29Make sure drug therapy is really needed. Some diseases should first be treated with sensible lifestyle changes, therapies and other proven effective non-drug remedies. Insomnia, constipation, high blood pressure, anxiety, situational depression may respond very well to non-drug treatments [79-83].

30Discuss with your doctor all treatment options.

31Weigh the benefits and risks, making the choice. If drug is the preferred treatment for the medical problem, try to choose the most safest and effective one. Think about the helpful effects as well as the possible unwanted effects. You must decide what risks you can and will accept in order to get the benefits you want. For example, if facing a life-threatening illness, you might choose to accept more risk in the hope of getting the benefits of a cure or living a longer life. On the other hand, if you are facing a minor illness, you might decide that you want to take very little risk. The expert advice from your doctor and the information you give him can help guide in making the decision that is right for you.

32Avoid treating diseases with drugs that are not effective for those problems.

• Antibiotics are often overprescribed for conditions that, because of their viral origin, do not respond to these drugs [84].
• Calcium channel blockers have not been established as effective for treating people who have had a recent heart attack. The study shows that this prescribing pattern actually did indirect damage to patients because their use was replacing the use of beta-blockers, drugs shown to be very effective for reducing the subsequent risk of death or hospitalization following a heart attack [15].

33Start the medication with as low a dose as possible. A lower dose will cause fewer adverse effects, which are almost always dose-related.

34Inform the doctor if medication doesn't seem to be effective. No medication has 100% efficacy rate. If you have no improvement, your doctor might change the dosage or change the medication.

35Eliminate the unnecessary drugs. At least every three to six months, regularly review with your doctor the need to continue each drug being taken. For many drugs, such as sleeping pills, tranquilizers, antidepressants, and antibiotics, this reevaluation should be more frequent. You and your doctor should also discuss the possibility of lowering the dose. Eliminating a drug that is no longer necessary not only eliminates the side effects, but may also save your money.

36Pay special attention to the active ingredients if you are taking more than one OTC or prescription drug to avoid taking too much of a particular ingredient, which can be dangerous. Many medications contain the same active ingredient. Never take more than one drug with the same active ingredient unless your doctor specifically tells you to.

37Know about serious adverse drug reactions and medications associated with them:

• Peptic ulcers, bleeding from the stomach: corticosteroids, Non-steroidal anti-inflammatory drugs (NSAIDs), anticoagulants
• Anemia: Chloramphenicol, antimalarial and antituberculous drugs.
• Decreased production of white blood cells, with increased risk of infection: clozapine
• Liver damage: acetaminophen (excessive doses), antituberculous drugs (isoniazid), allopurinol, sulfamethoxazole/trimethoprim, NSAIDs (diclofenac, nimesulide, piroxicam), flutamide, phenytoin, fluconazole [92-98].
• Kidney damage: ACE inhibitors, Nonsteroidal anti-inflammatory drugs (repeated use of excessive doses), aminoglycoside antibiotics, vancomycin, cyclosporine [99-101].
• Rhabdomyolysis: rabeprazole, fluoroquinolone antibiotics, antidepressants (bupropion, citalopram, venlafaxine), statins, antipsychotics (clozapine, risperidone, quetapine) [1]
• Angioedema (Quincke's edema): fluoroquinolone antibiotics, Proton pump inhibitors, Angiotensin 2 receptor antagonists, antipsychotics, orlistat [1]
• Pseudomembranous colitis: antibiotics [1].

38Use online side effects checking tools. If you are taking several medications and develop any new symptom, use online tools that allow you to check what medication could cause the symptom to appear, e.g. Side Effects Index

39Genetic differences in drug metabolism (genetic polymorphisms). Genetic variations alter the drug metabolizing enzymes, making them either less effective or more effective. Thus, people who carry these variations are either slow metabolizers or fast metabolizers of the drugs handled by that enzyme. A drug may become more highly concentrated in the bloodstream of poor metabolizers, which can result in stronger or longer drug action and toxic effects. Conversely, the drug is less concentrated in the bloodstream of fast metabolizers, resulting in weaker or briefer drug action or side effects. For example, Slow-acetylator status (polymorphism of N acetylation) of N-acetyltransferase 2 gene is a significant risk factor for antituberculosis drug-induced hepatitis [91].

40Certain medication may effect your ability to drive. Reactions that may make it more difficult for you to drive a car safely include:

• sleepiness
• blurred vision
• dizziness
• slowed movement
• fainting
• inability to focus or pay attention
• nausea

Food-drug interactions are changes in a drug's effects caused by food (including beverages) consumed during the same time period.

41Know when the medication should be takean: before, during, or after food. Food can increase, decrease, or delay the absorption of numerous drugs. Food-drug interactions can lead to a treatment failure or a toxic effects of drug therapy. Examples of drugs whose absorption is decreased when taken with food include penicillin, tetracycline, erythromycin, levodopa, phenytoin, and digoxin. Drugs whose absorption increases when taken with food include spironolactone, lovastatin, griseofulvin, and itraconazole [85].

42When taking medicine with food or around a meal time is not recommended, take medicine one hour before meal/food or two hours after meals or eating food.

43Learn about common food-drug interactions:

• Dairy products: fluoroquinolone antibiotics (ciprofloxacine, levofloxacin, ofloxacin, norfloxacin), laxatives (bisacodyl, senna).
• Grapefruit juice interacts with antiarrhythmics, calcium channel blockers, PDE-5 inhibitors (Viagra, Levitra, Cialis), statins (simvastatin (Zocor), lovastatin (Mevacor)), psychiatric medications (duloxetine (Cymbalta), olanzapine (Zyprexa), quetapine (Seroquel)), estrogen, oral contraceptives, allergy medications (Flonase, Seldane, Hismanal). The juice modifies the body's way of metabolizing the medication, affecting the liver's ability to work the drug through a person's system.
• High in vitamin K (fish, liver, spinach, cabbage, brussels sprouts, green leafy vegetables) should not be taken in great quantities while taking warfarin (Coumadin). These vegetables could totally negate the affects of the drug and cause blood clotting.
• Tyramine-containing food (aged cheese, fava beans, sauerkraut, beans, some beers, red wine, chocolate, pepperoni and overly ripe avocados) should be avoided by people taking MAO antidepressants. The interaction can cause a potentially fatal rise in blood pressure.

Many medications can interact with alcohol, leading to increased risk of illness, injury, or death. For example, it is estimated that alcohol-medication interactions may be a factor in at least 25% of all emergency room admissions [88].

Alcohol appears to interact with many drugs in many different and complicated ways. The combined use of alcohol and drugs may result in potentially harmful interactions especially when central nervous system depressants are involved. Often the mechanisms responsible for an adverse alcohol-drug interaction include inhibition of biotransformation and enhancement of the central depressant effects. Long-term ingestion of alcohol can lead to hepatic enzyme induction and in many instances to enhanced biotransformation of numerous substances, usually resulting in reduced therapeutic effectiveness [89].

44Avoid concurrent use of alcohol with medications.

45Know about common specific alcohol-drug interactions:

• Antibiotics (furazolidone, metronidazole) - Disulfiram reaction (flushed face, severe headache, shortness of breath, nausea, vomiting, weakness) [1].
• Antituberculous agents (ethionamide, isoniazid, cycloserine) - liver disease, seizures, psychotic reaction [1].
• Antiparkinsonism medications (tolcapone, amantadine) - increased sedation, potential for CNS effects such as confusion, dizziness, orthostatic hypotension [1].
• Antifulgals (griseofulvin, ketoconazole, itraconazole) - Disulfiram reaction (flushed face, severe headache, shortness of breath, nausea, vomiting, weakness) [1].
• Antihistamines (chlorpheniramine, diphenhydramine, meclizine, promethazine, cetirizine) - excessive sedation, additional imparement of CSN performance [1].
• Antihypertensive medications (ACE Inhibitors, Angiotensin 2 Receptor Antagonists, diuretics, Calcium channel blockers) - risk of orthostatic hypotension [1].
• Anticoagulants (warfarin) - acute alcohol consumption enhances warfarin's availability, increasing the patient's risk for life-threatening hemorrhages; chronic alcohol consumption reduces warfarin's availability, lessening the patient's protection from the consequences of blood-clotting disorders [1], [6].
• Anticonvulsants (valproic acid, phenytoin, topiramate) - deep sedation, additive CNS depression. Chronic drinking may decrease phenytoin availability, significantly reducing the patient's protection against epileptic seizures [1].
• Antidepressants - alcohol increases the sedative effect of tricyclic antidepressants [1], [7]. Venlafaxine, mianserin, moclobemide, and mirtazapine are associated with a risk of fatal toxicity, when are used with alcohol [90]. Concomitant use of duloxetine (Cymbalta) with alcohol can cause liver damage [1]. Alcohol consumption with MAO inhibitors is contraindicated, as it can result in increased sedation to dangerous level [1]. Bupropion is contraindicated in patients undergoing abrupt discontinuation of alcohol [1].
• Antidiabetic medications (sulfonylureas, insulin analogs, metformin) - risk of hypoglycemia, increased insulin effect [1].
• Antipsychotic medications (clozapine, olanzapine, haloperidol, risperidone, ziprasidone) - acute alcohol consumption increases the sedative effect of these drugs, resulting in impaired coordination and potentially fatal breathing difficulties [1], [6]. The combination of chronic alcohol ingestion and antipsychotic drugs may result in liver damage.
• Muscle relaxants (cyclobenzaprine, carisoprodol, metaxalone, methocarbamol) - increased sedation, depressed brain function [1].
• Narcotic pain relievers - the combination of narcotic analgesics and alcohol enhances the sedative effect of both substances, increasing the risk of death from overdose [1], [8].
• Non-narcotic pain relievers - alcohol can exacerbate the pain medication effects such as stomach bleeding and inhibition blood from clotting. Older persons who mix alcohol with large doses of aspirin are at particularly high risk for episodes of gastric bleeding. In addition, aspirin may increase the availability of alcohol, heightening the effects of a given dose of alcohol. Chronic alcohol ingestion activates enzymes that transform acetaminophen into chemicals that can cause liver damage, even when the drug is used in therapeutic amounts. These effects may occur with as little as 2.6 grams of acetaminophen in persons consuming widely varying amounts of alcohol [1], [9], [10], [12].
• Sedatives, hypnotics ("sleeping pills") (barbiturates, benzodiazepines, zolpidem). Benzodiazepines may cause severe drowsiness in the presence of alcohol, increasing the risk of household and automotive accidents. This may be especially true in older people, who demonstrate an increased response to these drugs. Acute alcohol consumption increases the availability of barbiturates, prolonging their sedative effect. Chronic alcohol consumption decreases barbiturate availability. In addition, acute or chronic alcohol consumption enhances the sedative effect of barbiturates at their site of action in the brain, sometimes leading to coma or fatal respiratory depression [1], [11].

46Be aware of the most common interactions with herbal products:

• Ginkgo biloba plus aspirin, warfarin (Coumadin), ticlopidine (Ticlid), clopidogrel (Plavix), dipyridamole (Persantine)
• St. John's wort plus antidepressants, oral contraceptives, cyclosporine, digoxin, methadone, simvastatin, tacrolimus, theophylline, warfarin [14]
• Ephedra plus caffeine, decongestants, stimulants
• Ginseng plus warfarin
• Kava plus sedatives, sleeping pills, antipsychotics, alcohol

Certain drugs are relatively safer than others, and the selection of the appropriate drug is very important. At least 5% of all birth defects are drug induced. Drugs that produce fetal abnormalities are called "dysmorphogens" or "teratogens" [86].

During the first 2 weeks after fertilisation and prior to full implantation, the embryo is thought to be resistant to any teratogenic effects of drugs. This is because there is no direct communication between maternal and embryonic tissue until after the placenta starts to form. The critical period with respect to teratogenic effects is during organogenesis. This starts at about 17 days after conception and is complete by 60 to 70 days. Exposure to certain drugs during this period (17 to 70 days) can cause major birth defects.

47Use the medication only if the benefits outweigh the risks. Whether or not you should take medicine during pregnancy is a serious question. A true indication must be present for the administration of any medication. Talk with your doctor about whether the benefits of taking a medication outweigh the risk for you and your baby. The effect of a drug on the fetus may not necessarily be the same as the intended pharmacological effect on the mother.

No drug should be considered 100% safe to the developing fetus, including topical preparations. Generally all drugs are contraindicated during pregnancy, especially during the 1st trimester. But If you don't take medicine that you need, this could harm both you and your baby. If a diabetic woman does not take her medicine during pregnancy, she increases her risk for miscarriage and stillbirth. If asthma or high blood pressure are not controlled during pregnancy, problems with the fetus may result.

48If you were taking drugs for a medical condition before pregnancy, discuss this with your doctor as soon as you are aware that you are pregnant. Although many drugs are not harmful to your baby’s development, there is a small number of drugs that could be very harmful. If you were exposed to a possibly harmful drug early in your pregnancy, you should seek prenatal counseling and testing to detect any developmental problems early. Your doctor may want to stop a drug during your pregnancy, or switch to a safer drug during that time.

49Do not stop any chronic medication on your own. If you stop taking the medication that you need, this can harm both you and your baby. Untreated disease such as diabetes or epilepsy may be very harmful to your baby’s development.

50Alcohol. Is there a "Safe" amount? Don’t drink alcoholic beverages until after your baby is born. Although heavy drinking has been linked to serious damage to a baby’s development (fetal alcohol syndrome), the exact amount of alcohol needed to produce this effect is not known [13], [16].

51Know about most dangerous medications for use in pregnancy: Some medication that may cause birth defects (with pregnancy category: Category X drugs are contraindicated in pregnancy because the risk to the fetus clearly outweighs any benefit. Category D drugs, are those whose therapeutic benefits may outweigh the risks.) [1]:

• ACE inhibitors (eg, captopril, enalapril) - D
• Androgens (eg, Danazol) - X
• Angiotensin II receptor antagonists (eg, losartan, valsartan) - D
• Anthelmentics
• Aminoglycosides (eg, gentamicin, streptomycin) - D
• Anticonvulsants (trimethadione, Valproic acid - D, phenytoin, and carbamezapine - D)
• Aspirin - D
• Benzodiazepines - D and X
• Birth control pills/hormone replacement therapy - X
• Colchicine - D
• Danazol - X
• Ergotamine - X
• Finasteride - X
• Danazol - X
• Fluconazole - C
• Folic acid antagonists (Phenytoin - D, Methotrexate - X)
• Laxatives
• Lithium - D
• Misoprostol - X
• Phenobarbital or methylphenobarbital - D
• Potassium iodine and medications that effect iodine levels (diatrizoate) - D
• Progestins - X (except megestrol and norethindrone - D)
• Raloxifene (Evista) - X
• Retinoic acid, isotretinoin (Accutane), acitretin (Soriatane), etretinate, topical tazarotene - X
• Statins (HMG-CoA reductase inhibitors) - X
• Tetracyclines - D
• Warfarin - X

52Drugs of doubtful safety or value, and drugs that are not normally used in neonates should never be considered. Safer, well-established drugs should be used if a need for therapy arises during breast feeding.

53Short acting drugs should be preferred to long acting or those with delayed excretion or accumulating effects.

54Once or twice-daily dosage is preferable to 4-6 hourly regimens.

55Breast-feed the baby before rather than just after taking the drug. Ingestion of medications just after nursing will allow a significant portion of the drug to be eliminated prior to the next feeding.

56Ask your doctor or pharmacist when the lowest amount of the medication will be in your system. Try to breastfeed when amounts are lowest. Usually this occurs right before it is time to take the next dose of the medication.

57Athough nearly all drugs are present in breast milk following maternal ingestion, few are absolutely contraindicated or should be avoided by nursing mothers (i.e., amiodarone, aspirin, barbiturates, benzodiazepines, carbimazole, combined oral contraceptives, cytotoxic drugs, ephedrine, and tetracyclines)

58Anything applied to your nipple (for instance, vitamin E oil) is likely to be absorbed by your infant. Do not assume that vitamin and mineral oils are harmless. Many reports suggest that too much of the oil can harm your baby.

59Know facts about commonly used medications:

• Paracetamol is not known to cause any side effects in the infant and could be used safely if indications arise.
• Aspirin is excreted in moderate amounts and could cause a bleeding tendency in the infant. Although this is a minimal risk, aspirin should be avoided. Single occasional doses of a morphine and aspirin combination could be used without adverse effects, but continuous medication could produce an accumulative effect and should be avoided.
• Antibiotics. Penicillins, cephalosporins and macrolides are safe and thus the preferred drugs if indications for their use arise. Tetracyclines and sulphonamides should not be used while breast feeding. Tetracyclines may cause staining of the teeth and abnormalities of bone growth, and sulphonamide may cause jaundice in infants leading to kernicterus.
• Bromocriptine suppresses lactation. Contraindicated during breast feeding.
• Chloramphenicol affects the bone marrow. Contraindicated during breast feeding.
• Metronidazole should be used with caution, as it may produce decreased appetite, vomiting and, rarely, blood dyscrasia.

60Know your child’s weight since many medications are dosed by weight.

61Never give aspirin to a child or teenager who has or is recovering from chickenpox, flu symptoms (nausea, vomiting or fever), or flu. In such patients aspirin may be associated with an increased risk of Reye syndrome, a rare but serious illness.

62Never tell a child medication is candy. As soon as your back is turned, children will sometimes try to get as many of these candies into their mouths as possible. Teach children that medications can be dangerous if misused.

63Be as precise as possible in your measurements. Teaspoons vary greatly in size. When most doctors prescribe a teaspoon, they mean to prescribe five cubic centimeters of medication. If the medicine came with a measuring device, such as a dropper, medicine cup, or dosing spoon, only use it and do not substitute another device when administering it to your child. Many pharmacies sell small plastic measuring devices or give them away when a prescription is filled.

64Be aware of your medication needs and be prepared for any emergency. Store 3-5 days supply of medications that are important to your health. Include any medications used to stabilize an existing medical condition or keep a condition from worsening or resulting in hospitalization, such as medications for asthma, seizures, cardiovascular disorders, diabetes, psychiatric conditions, and thyroid disorders. Carry these with you, if possible, in a purse or briefcase in labeled containers.

65Refill your prescriptions while you still have at least a 5-7 day supply of medications left. Keep in mind that some sources, such as mail-order pharmacies, have a longer lead time to refill.

Medications must be taken properly to ensure its safety and effectiveness Misusing medications can have serious results. Up to half of Americans taking prescription medications do not take them as prescribed, according to the FDA. Some persons may skip doses or take extra pills in an attempt to intensify the drug's effects. Others may feel better and stop taking a prescription before it's finished, only to pick it up again months or years later when similar symptoms arise.

66Follow your doctor's instructions on how to take your medication.

67Learn how to take the medication:

• What is your dose?
• How long should you take the medication?
• Should you take the drug before, during, or after meals?
• What should the timing be between each dose?
• What should you do if you miss a dose or use too much by mistake?
• Are there any special directions for using the medication?

68Don't skip or reduce the doses. Missed doses of glaucoma medicine, for example, can lead to optic nerve damage or blindness. Missed doses of heart medicine can lead to cardiac arrest. It is not valid to assume that taking half of the regular dose will provide half of the therapeutic effects. Indeed, a smaller dose may not provide any benefit whatsoever.

69Don't take extra pills.

70Finish the entire course of medication. Never stop taking medicine the doctor has told you to finish just because symptoms disappear. Stopping taking a prescription (such as antibiotics or anti-rejection drugs for transplant patients) before it's finished often occurs when a person begins to feel better or symptoms disappear. However, if the entire course of antibiotics is not finished, the infection may not be completely killed, and even if a transplant patient feels "used" to a transplanted organ, the body may not.

71Learn how to discontinue the use of the medication. Many medications (e.g. antidepressants, corticosteroids) should not be stopped abruptly.

72If you have a poor compliance and are prescribed the medication with frequent dose regimen, ask your doctor if there is a way to take the medicine less often during the day, such as switching to a higher dose or a different medicine that doesn't require as many doses.

73If you forget to take medicines on time, ask your pharmacist about medication reminder devices such as calendars, mini-alarms or blister packages (plastic, sealed bubbles). For more complicated regimens, pill boxes with various compartments (for meals, days or weeks) can help. Pill boxes are also useful for people who have trouble opening pill bottles.

74With liquid medication, use only the measuring device that came with it. Many household teaspoons and tablespoons are not accurate. If you don’t have a medicine device for measuring your liquid medicine, ask for one at the pharmacy.

75Do not chew, crush or break any capsules or tablets unless instructed by your doctor. Some medications are absorbed too quickly when chewed or crushed which could have an effect similar to taking an overdose.

76Stand or sit upright for at least five to ten minutes after taking the medication - gravity can help the medication reach your stomach.

77Check expiration dates. Do not use prescription or over-the-counter drugs, vitamins or herbal remedies beyond the expiration date. After the expiration date, the medicine may lose its potency. Expired drugs are at greater risk of losing potency than causing harm. In general, expiration dates are shorter on liquid medications and longer on solid ones.

78Avoid taking medications in the presence of children, as they often try to imitate adults.

79Unused medication. Many sources recommend to throw out unused medication. However, if you expect you may need the same medication soon, it makes sense to reserve the rest of the drug. It may help you to save the money. So, if you deside to save the rest of unused medicine for future use "just in case" follow the next steps:

• Save the medication in the original container with the cap closed. It will help to identify the drug over the time and provide proper storage conditions.
• When use the old medication, check expiration date. In case you can't find the expiration date, throw out the drug.

80Clear out your medicine cabinet at least once a year. Dispose of medicines that are old, no longer in their original containers, with illegible labels or that have changed colour, smell or taste.

Storage is important for all drugs. Certain medications are very sensitive to heat, humidity, light, oxygen and moisture. If a medication is stored improperly, even for a short time, the medication may break down, rendering it less effective. Further, when medications degrade they may not be able to dissolve properly, and won't be able to be used correctly by your body.

Medications break down more quickly in unstable environments. Incredibly, the bathroom, where, according to the survey, 49 percent of Americans store their medications, is a poor choice because of fluctuating temperatures and humidity. The kitchen, where 29 percent keep their drugs, is a problem for the same reasons. It’s also important to remember that medicine often comes in colored vials to keep out light, which can degrade some drugs. A bedroom, where the temperature is consistent and where medications can be kept out of humidity and sunlight is a better option.

81Read the medication's label and store accordingly.

82Keep all medicines in their original containers, so you don't confuse one medicine with another, lose the instructions, or take outdated medicine.

83Unless instructed otherwise, keep medication away from heat, light and moisture.

84Never store medicine in the bathroom. Most people tend to store drugs in one of the hottest, most humid places in the house: the bathroom. The bathroom is probably the last place they should be kept. The kitchen may be a problem for the same reasons. A bedroom, where the temperature is consistent and where medications can be kept out of humidity and sunlight is a better option.

85Keep all medications out of children's reach. Some medicines, such as iron supplements, are very toxic to children. Use child-resistant caps, and never leave containers uncapped.

86Unless label instructs you otherwise, do not store medications refrigerated.

Many medications are expensive and people hate to waste them. To save money and avoid a trip to the doctor for a new prescription, many people do take expired drugs.

In general, drugs expiration date is 2-5 years from production date. This means that before expiration date, right conserved drugs can maintain at least 90% of their efficacy. The expiration date does not necessarily suggest that the medication will be ineffective, or even harmful. For example, if a company chooses a two year expiration date, it does not have to test beyond that for prolonged effectiveness.

Drug efficacy begins to reduce from the moment it is manufactured; it is not in anyway spontaneous after the expiry date. Medications probably continue to be effective at least one to two years after the expiration date, and maybe as long as 10 to 15 years later [23].

87Factors that negatively modify storage condition: light, oxygen, moisture, extreme temperatures.

88Do not use the following expired medications. Many drugs have a narrow therapeutic index and little decreases in the pharmacological activity can result in severe consequences for patients. Respect expiration date is obligatory for the following medications:

• Anticonvulsants (narrow therapeutic index)
• Dilantin, phenobarbital (very quickly lose potency)
• Nitroglycerin (very quickly lose potency)
• Warfarin (narrow therapeutic index)
• Procan SR® (sustained release procainamide)
• Theophylline (very quickly lose potency)
• Digoxin (narrow therapeutic index)
• Thyroid preparations
• Paraldehyde
• Oral contraceptives
• Epinephrine (very quickly lose potency)
• Insulin (very quickly lose potency)

89Liquid medications. Drugs in liquid form (solutions and suspensions) are not as stable as solid dosage forms (tablet, powder, capsule). Suspensions are especially susceptible to freezing. Injectables, that have become cloudy or discolored or show signs of precipitation should not be used. Drugs prepared by addition of a solvent before dispensing or administration (such as suspensions of antibiotics for oral use or lyophilized drugs in vials for parenteral use) tend to be relatively unstable in the liquid state. With ophthalmic drugs, the limiting factor may not be the stability of the drug, but the continued ability of the preservative to inhibit microbial growth.

90Toxicity. Contrary to common belief, there is little scientific evidence that expired drugs are toxic. There are virtually no reports of toxicity from degradation products of outdated drugs. According to The Medical Letter the only report of human toxicity that may have been caused by chemical or physical degradation of a pharmaceutical product is renal tubular damage that was associated with use of degraded tetracycline (GW Frimpter et al, JAMA 1963; 184:111). Since then, tetracycline products have been changed to eliminate the problem [24]. The lack of other reports of toxicity from expired medication is reassuring, however expired medication toxicity is not a well-researched field.

91Potency. How much of their potency medications retain varies with the drug and the storage conditions, especially humidity. However, some drugs stored under optimal conditions retain 90% of their potency for about 5 years after the expiration date [23].

92Factors to consider in deciding whether to use an expired medication:

• Dosage formulation (liquid are less stable).
• Package-type, container closure system.
• Storage conditions. Medications do retain their effectiveness longer if they are kept unopened.
• Length of time between initial manufacture and final use.
• Appearance of medication. Do not use if: tablets are brittle or breaking apart; tablets or capsules have loss of sheen; tablets or capsules are soft; emulsions or suspensions remain separate despite shaking; injectables appear discolored or a precipitate has formed. With aspirin, it's easy to tell if it's "going bad": the stronger it smells, the less effective it is. Never take medicine that seems suspicious in some other way.

93Predominance of transmural myocardial infarctions occurs between 6 am and 12 noon. Blood pressure is lowest between 2 am and 4 am. At 6 am, blood pressure begins to rise dramatically. Thus, increased stress on the heart in the early morning when blood pressure begins to rise is associated with increased likelihood of having a myocardial infarction. Angina also follows a similar pattern [26].

94Histamine is released by mast cells in the late afternoon. This means that patients are more likely to have allergic reactions in early afternoon or evening. Therefore, drugs with allergic properties should be given earlier in the day. Also, antihistamines are more effective when taken at 7 pm than when taken in the morning [26].

95Epileptic seizures occur more frequently when body temperature is higher. Researchers are starting to look at when analeptics should be given based on temperature [26].

96Alcohol is absorbed more quickly in the morning but has less effect. Therefore, people can drink more in the morning with fewer side effects [26].

97Aspirin is a very effective antiplatelet drug, but should be given in the morning. Bioavailability in the morning is twice as high as in the afternoon [26].

98Digoxin should be taken in the morning. Side effects increase by 40% when taken at night [26].

99Diuretics work best from 6 am to 12 noon. Furosemide (Lasix) and thiazide diuretics don't work as well in the afternoon or evening [26].

100The absorption of ibuprofen is greater in the morning, but is also associated with more intolerance if taken at this time. It is better to take NSAIDs in the late afternoon or evening [26].

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