From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should

From Grapefruit to From Grapefruit to Glaucoma:Glaucoma:

Interactions and Side Interactions and Side Effects You Should Be Effects You Should Be

Aware OfAware OfRichard L. Ogletree, Jr,

Pharm.D.

ScopeScope

Drug related morbidity and mortality - estimated yearly cost in ambulatory setting of $76.6 billion.

Most of this is due to hospitalization 8.76 million admissions $47.4 billion

28% of hospitalizations due to drug related causes

Arch Int Med 1995;155:1949

Hospitalized PatientsHospitalized Patients 1994 - estimated 33.1 million hospital

admissions Estimated 2.2 million serious ADR’s (1

in 15 patients) Estimated 106,000 fatal ADR’s (1 in 315

patients) 4th to 6th leading cause of death in U.S.

Lazarou, et al. JAMA 1998;279(15):1200

DefinitionsDefinitions

ADR - FDAADR - FDA

Any adverse event associated with the use of a drug in humans, whether or not considered related, including an adverse event occurring with the use in professional practice; from accidental or intentional overdose, from abuse, from withdrawal, or a failure of expected activity

ADR - WHOADR - WHO

Any response to a drug that is noxious and unintended and that occurs at doses used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiological function

ADE - Adverse Drug ADE - Adverse Drug EventEvent

Includes medical errors

Categories of ADR’sCategories of ADR’s

Predictable or Type A (augmented) side effects toxic effects

Non-predictable or Type B (bizarre) hypersensitivity responses idiosyncratic effects

Side EffectsSide Effects

A result other than the one desired from the agent diphenhydramine - drowsiness nitroglycerin - headache prazosin - nasal stuffiness

Toxic EffectsToxic Effects

Direct cellular function alteration or damage colchicine - GI upset, myopathy digoxin - heart block aminoglycosides - nephrotoxicity

HypersensitivityHypersensitivity

Reacting to substances in amounts not causing the reaction in most individuals prior exposure is necessary often independent of dose often associated with cell bound IgE

antibodies often associated with elevated

eosinophil counts (>300)

HypersensitivityHypersensitivity

Could range from rash to anaphylaxis sulfonamide allergies penicillin allergies many hepatotoxicities

Idiosyncratic EffectsIdiosyncratic Effects

“Abnormal susceptibility to some drug, protein, or other agent that is peculiar to the individual”

Prior exposure not necessary Often genetic

acetylator status (INH, procainamide) Glucose 6PD deficiency agranulocytosis with chloramphenicol

Assessment of ADR’sAssessment of ADR’s

Temporal relationship Dechallenge Rechallenge Confounders

Can Influence ADR’sCan Influence ADR’s

Age Weight Race Sex Pregnancy Concomitant diseases Other drugs or food

Drug interactionsDrug interactions

Pharmacological or clinical response to the administration of a combination of drugs is different from that anticipated when drugs are given alone

More simply put...More simply put...

When the effects of one drug are changed by presence of another drug, food, drink, or environmental chemical agent

Net effect could be ...Net effect could be ...

Enhanced response to one or more of the components

Antagonism of effect of one or more of the components

Idiosyncratic effect

Important:Important:

Drug interactions could be desirable multiple mechanisms of action decreasing necessary dose decreasing side effects antidotes

Types of Drug InteractionsTypes of Drug Interactions

Pharmaceutical Pharmaceutical incompatibility - incompatibility - including including in vivo bindingin vivo binding

IV admixture incompatibility Tetracyclines and Ca++ or iron Fluoroquinolones and aluminum or iron Phenytoin suspension and NG tube

feedings Olestra or orlistat and fat soluble

vitamins?

Receptor site Receptor site interactioninteraction

Alpha blockers and nasal decongestants

Naloxone and opioids Clonidine in opiate withdrawal Vitamin k and coumadin Epinephrine and beta blockers Flumazenil and benzodiazepines

Influence of same Influence of same physiological systemphysiological system

Warfarin and NSAIDS Aminoglycosides and

neuromuscular blockers Beta blockers, digoxin, verapamil,

diltiazem Multiple anti-hypertensives

Changes in electrolytes Changes in electrolytes or fluid balanceor fluid balance

ACE inhibitors and K+ Lithium and high sodium intake Lithium and low sodium diet Ampho B and diuretics

Absorption interactionsAbsorption interactions

Antacids and drugs Grapefruit juice Doxycycline and digoxin Erythromycin and sulfasalazine Omeprazole and ketoconazole Binding in GI tract

DistributionDistribution

Protein binding mostly theoretical generally transient warfarin and phenytoin

Tissue binding quinidine and digoxin

Drug metabolism - Drug metabolism - inductioninduction

Inducers phenytoin phenobarbital carbamazepine rifampin cigarette smoke St. John’s wort

Drug metabolism - Drug metabolism - inductioninduction

Be careful with oral contraceptives HRT cyclosporine

Drug metabolism - Drug metabolism - inhibitioninhibition

Inhibitors azole antifungals

ketoconazole itraconazole

macrolide antibiotic erythromycin clarithromycin

cimetidine

Drug metabolism - Drug metabolism - inhibitioninhibition

More inhibitors SSRI’s

fluvoxamine paroxetine fluoxetine

nefazodone fluoroquinolones amiodarone

Grapefruit JuiceGrapefruit Juice

Caused by furanocoumarin fractions

Takes place in GI tract Inhibition of CYP450 1A2 & 3A4 Prevents GI metabolism Increases absorption Increased peak

Grapefruit Juice Grapefruit Juice InteractionsInteractions

Calcium channel blockers (felodipine, nisoldipine, nifedipine, verapamil)

Cyclosporine Midazolam (oral) Cisapride Simvastatin, lovastatin

Predicting Grapefruit Predicting Grapefruit Juice InteractionsJuice Interactions

Absorption Bioavailability CYP 450 esp. 3A4 metabolism Look on insert

HMG - CoA Reductase HMG - CoA Reductase Inhibitors (“statins”)Inhibitors (“statins”)

Lovastatin (Mevacor®) Pravastatin (Pravachol®) Simvastatin (Zocor®) Fluvastatin (Lescol®) Atorvastatin (Lipitor®) Rosuvastatin (Crestor®)


Lower cholesterol Inhibit rate limiting reaction in

mevalonate pathway Other mevalonic acid products

dilochol (liver, retina) ubiquinone (muscles)

Concerns with “Statins”Concerns with “Statins”

Liver problems Concern with ALT or AST > 3X ULN

Muscle problems Concern with CK > 10X ULN

Consider ubiquinone supplementation in selected patients

Liver Monitoring with Liver Monitoring with “Statins”“Statins”

Fluvastatin (Lescol®) bl, 12 wks Simvastatin (Zocor®) bl, 3 mo. (80 mg), 6 mo. 12 mo. Atorvastatin (Lipitor®) bl, 12 wks, 2X/year Lovastatin (Mevacor®) bl, 6 wks, 12 wks, 2X/year Rosuvastatin (Crestor®) bl, 12 wks, 2X/yearNote: This is with initiation and with each dose increase. Pravastatin (Pravachol®) bl, prior to dose increase and

when “clinically indicated”


Drugs which increase levels can increase the chance of myopathy or rhabdomyolysis Cyclosporin Gemfibrozil Niacin Erythromycin, Clarithromycin Itraconazole Nefazodone (Serzone®)


Situations which predispose to myopathy could increase the chance of myopathy or rhabdomyolysis major surgery severe acute infection trauma seizures electrolyte disturbances hypotension


Concerns unexplained muscle pain accident hospitalization?

Theoretical concerns Metformin Stavudine and other NRTI’s weight-lifting?

Zocor (simvastatin): Label Zocor (simvastatin): Label Change - New Restrictions, Change - New Restrictions, Contraindications, and Dose Contraindications, and Dose

LimitationsLimitations

Posted:06/08/2011

FDA notified healthcare professionals that it is recommending limiting the use of the highest approved dose of the cholesterol-lowering medication simvastatin (80 mg) because of increased risk of muscle damage. Patients taking simvastatin 80 mg daily have an increased risk of myopathy compared to patients taking lower doses of this drug or other drugs in the same class. This risk appears to be higher during the first year of treatment, is often the result of interactions with certain medicines, and is frequently associated with a genetic predisposition toward simvastatin-related myopathy. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure which can be fatal. FDA is requiring changes to the simvastatin label to add new contraindications (should not be used with certain medications) and dose limitations for using simvastatin with certain medicines.

SimvastatinSimvastatin

• Contraindicated Itraconazole Ketoconazole Posaconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone Gemfibrozil Cyclosporine Danazol


• Contraindicated Itraconazole Ketoconazole Posaconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone Gemfibrozil Cyclosporine Danazol


10 mg/day Diltiazem Verapamil

20 mg/day Amiodarone Amlodipine Ranolazine

Grapefruit juice Avoid > 1 quart/day

Lovastatin - Feb. 28, Lovastatin - Feb. 28, 20122012

Strong CYP3A4 inhibitors are contraindicated• Avoid

Cyclosporine Gemfibrozil

• 20 mg/ day Danazol Diltiazem Verapamil

• 40 mg amiodarone

Grapefruit juice Avoid > 1 quart/day

Also from Feb. 28, 2012Also from Feb. 28, 2012

Added to warnings memory problems new onset diabetes

Removed - recommendation for routine liver enzymes -

Liver injury from statins is rare, and monitoring does not seem to be

effective in predicting or preventing such damage.

Atorva Fluva Pitava Lova PravaRosuv

aVytori

n*Simva

%↓ LDL-C

----- 40 mg 1 mg 20 mg 20 mg ----- ----- 10 mg 30%

10 mg 80 mg 2 mg40 or 80 mg

40 mg ----- ----- 20 mg 38%

20 mg ----- 4 mg 80 mg 80 mg 5 mg10/10

mg40 mg 41%

40 mg ----- ----- ----- 10 mg10/20

mg80 mg 47%

80 mg ----- ----- ----- 20 mg10/40

mg----- 55%

----- ----- ----- 40 mg10/80

mg----- 63%

*No incremental benefit of Vytorin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.

QuinolonesQuinolones Photosensitivity Drug interactions Rash Dizziness Seizure Insomnia Loss of glycemic control Tendon rupture

Quinolones - Tendon Quinolones - Tendon RuptureRupture

More common in 60 y/o and older Median of 6 days until onset Achilles most common Often bilateral Most recover by 2 months Stop at first sign of tendon pain

inflammation, or weakness Use care in weightlifters?

Quinolones - Tendon Quinolones - Tendon DisorderDisorder

Case-control study - n = 46,766 Adjusted relative risk > 60 years old

current use OR 3.5 (2.3 - 5.3)

concurrent steroids OR 6.2 (3.0 - 12.8)

recent or past use ns < 60 years old ns

van der Linden, et al. BMJ 2002;324:1306-1307

TetracyclinesTetracyclines

Photosensitivity Interaction with polyvalent cations Tooth staining Increased intracranial pressure (ICP) Also called BIH (Benign Intracranial

Hypertension) or Psuedotumor Cerebri

Tetracyclines - Tooth Tetracyclines - Tooth StainingStaining

Tetracycline - during tooth formation

Binds to calcium Cervical third of tooth (gingival

margin) Avoid during pregnancy Avoid in children

Tetracyclines - Tooth Tetracyclines - Tooth StainingStaining

Minocycline - after tooth eruption Incisional edge, middle third Binds to iron? Binds to glycoproteins oxidizing to form

quinone? > 100 mg/day > 1 month duration 3 – 6 % incidence

Minocycline - Tooth Minocycline - Tooth StainingStaining

PreventionPrevention Give an antioxidant Give lower doses 100 mg/day for 2 weeks, then 50

mg/day

Tetracyclines - BIHTetracyclines - BIH

Most common with minocycline Also seen with tetracycline and

doxycycline More common in normal weight

(idiopathic more common in obese) More common in adolescent and

young adult women

BIH BIH The diagnostic criteria are:

Increased intracranial pressure (> 200 mm water) Normal neurological examination except for papilledema

and/or sixth nerve palsy No mass or ventricular enlargement on imaging Normal CSF protein and white cell count No clinical or imaging evidence of venous sinus

thrombosis There may be decreased visual acuity and visual field

defects.


Not associated with dose Often occurs in first 2 to 4 weeks

of therapy Other drugs causing BIH

Vitamin A analogs (isotretinoin) Steroids (esp in withdrawal)


Ask about headaches tinnitis blurred vision double vision

Check for papilledema

LevothyroxineLevothyroxine Very commonly used Hypothyroidism

primary secondary

Weight loss - not a good idea Anemia predisposes to intolerance

watch for tachycardia, palpitations, nervousness

correct low Hct (esp if below 28) before starting

start low 25 mcg or less

Levothyroxine Levothyroxine interactionsinteractions

Calcium Iron (including prenatal vitamins or

other vitamin/mineral preps) Soy protein

all decrease absorption separate by at least 2 hours

SSRI’sSSRI’s Anxiety Insomnia Sexual dysfunction Withdrawal Interaction with DM cough preps Tooth grinding GI bleeds

SSRI withdrawalSSRI withdrawal

Disequilibrium dizziness vertigo ataxia swimming or spaced out feeling impaired coordination

SSRI withdrawalSSRI withdrawal GI disturbances

nausea vomiting diarrhea anorexia

Flu-like symptoms

SSRI withdrawalSSRI withdrawal Sensory disturbances

auditory hallucinations paresthesias electrical shock sensations

CNS symptoms agitation confusion headache lethargy

SSRI withdrawalSSRI withdrawal Sleep disturbances

insomnia nightmares vivid dreams

relapse of depression

SSRI withdrawal -SSRI withdrawal -most commonmost common

Dizziness Nausea Lethargy Headache

SSRI withdrawal SSRI withdrawal

Onset - 1 to 5 days after disruption (longer for fluoxetine)

Duration - 1 to 3 weeks Prevention - slow taper of meds Ginger has been helpful with

nausea and vertigo

SSRI - DM interactionSSRI - DM interaction

Dextromethorphan D-isomer of levorphanol Cough suppressant NMDA antagonist Decreases glutamate excitability

DextromethorphanDextromethorphan

Cough/cold preps Adjuvant for pain management

(including neuropathic pain) Decrease opioid tolerance Interacts with MOAI’s Interacts with SSRI’s

Serotonin syndromeSerotonin syndrome

Mental status changes Tremor Restlessness Incoordination Shivering Increased temperature

Serotonin syndromeSerotonin syndrome

Diaphoresis Hyperreflexia Myoclonus Diarrhea Convulsions Could be fatal

SSRI - DM interactionSSRI - DM interaction

If needing a cough suppressant use:

Benzonatate Carbetapentane combinations

SSRI Induced BruxismSSRI Induced Bruxism

Often nocturnal More common in women Probably dopaminergic (similar to

neuroleptics) 2 to 4 weeks from starting therapy

(reported range - 1 week to 11 months)

Sometimes, first noticed by dentist

SSRI Induced BruxismSSRI Induced Bruxism

Ask about/look for muscle tension headache joint pain (tmj) muscle pain (chewing muscles) masseter hypetrophy

SSRI Induced Bruxism - SSRI Induced Bruxism - ManagementManagement

Changing agents - probably not helpful

Decrease dose of SSRI Buspirone

5 - 30 mg usually hs dosing should have an effect in 1 to 4 weeks

SSRI’s and GI BleedsSSRI’s and GI Bleeds

SSRI antidepressants OR 3.0 (2.1 - 4.4) most likely - trazodone

Non SSRI antideps OR 1.4 (1.1 - 1.9)

Abajo, et al. BMJ 1999;319:1106-1109

SSRI’s and GI BleedsSSRI’s and GI Bleeds

Not adjusted for NSAID use SSRI antidepressants OR 2.6 (1.7 -

3.8) NSAID’s OR 3.7 (3.2 - 4.4) SSRI + NSAID OR 15.6(6.6 -

36.6)

Abajo, et al. BMJ 1999;319:1106-1109

8/24/20128/24/2012Abnormal heart rhythms Abnormal heart rhythms

associated with high doses associated with high doses of Celexa (citalopram of Celexa (citalopram

hydrobromide)hydrobromide)

The U.S. Food and Drug Administration (FDA) is informing healthcare professionals and patients that the antidepressant Celexa (citalopram hydrobromide; also marketed as generics) should no longer be used at doses greater than 40 mg per day because it can cause abnormal changes in the electrical activity of the heart. Studies did not show a benefit in the treatment of depression at doses higher than 40 mg per day.

Maximum dose - 40 mg/day due to prolongation of QT interval

Max of 20 mg/day 60 YO and older liver impairment poor CYP2C19 metabolizers taking cimetidine (Tagamet)

Not recommended for CHF patients bradyarrhythmias, concomitant use of medications that prolong the QT

interval Monitor ECGs and electrolytes Discontinue if patient has persistent QTc

measurements of > 500 ms.

ZyvoxZyvox

The U.S. Food and Drug Administration (FDA) has received reports of serious central nervous system (CNS) reactions when the antibacterial drug linezolid (marketed as Zyvox) is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications).

LinezolidLinezolid Inhibits monoamine oxidase A Results in decreased serotonin metabolism Serotonin toxicity = Serotonin syndrome Should avoid linezolid in patients taking

serotonergic drugs unless treating: VRE Noscomial pneumonia Complicated skin and skin structure

infections (including MRSA)

Emergent cases Use alternate therapy for linezolid Stop serotonergic drug and monitor

patient for CNS toxicity for: Two weeks (five with fluoxetine) 24 hours after last dose of linezolid whichever comes first

Non-emergent cases D/C serotonergic drug 2 weeks before

starting linezolid (5 weeks for fluoxetine) Resume serotonergic drug 24 hours after

last dose of linezolid Educate patient of signs and symptoms

of Serotonin Syndrome Report adverse events to FDA MedWatch

Serotonergic Psychiatric Serotonergic Psychiatric MedicationsMedications

SSRIs SNRIs Tricyclics MAOIs

Other: Amoxapine Maprotiline Nefazodone Trazodone Buproprion Buspirone Vilazodone

Serotonin Syndrome Serotonin Syndrome SymptomsSymptoms

Tremor Altered mental status Clonus Muscular hypertonicity hyperthermia

7/26/20117/26/2011Serious CNS reactions Serious CNS reactions

possible when methylene possible when methylene blue is given to patients blue is given to patients

taking certain psychiatric taking certain psychiatric medicationsmedications

The U.S. Food and Drug Administration (FDA) has received reports of serious central nervous system (CNS) reactions when the drug methylene blue is given to patients taking psychiatric medications that work through the serotonin system of the brain (serotonergic psychiatric medications). Methylene blue is commonly used in diagnostic procedures and is also used to treat a number of medical conditions.

Methylene blueMethylene blue

Monoamine oxidase inhibitor properties

Urgent treatment of: Methemoglobinemia Ifosfamide-induced encephalopathy Cyanide poisoning

AlsoAlso

Urinary medications UTA Urogesic blue

Antihistamine/Antihistamine/DecongestantDecongestantCombinationsCombinations

Newer antihistamines Less sedation Long duration of activity Good safety profiles

Antihistamine/Antihistamine/DecongestantDecongestantCombinationsCombinations Same decongestants (usually

pseudoephedrine) Increased heart rate Increased blood pressure Prostate disturbance Decreased appetite Anxiety Insomnia

Decongestant ProfilesDecongestant Profiles

050

100150

200250300

350400

450500

3.9 4.4 5 7

Claritin D 12Zyrtec DAllegra DClaritin D 24

3/12/20133/12/2013Azithromycin (Zithromax Azithromycin (Zithromax or Zmax) and the risk of or Zmax) and the risk of potentially fatal heart potentially fatal heart

rhythmsrhythms

The U.S. Food and Drug Administration (FDA) is warning the public that azithromycin (Zithromax or Zmax) can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.

Patients at particular risk for developing this condition include those with known risk factors such as:

existing QT interval prolongation low blood levels of potassium or magnesium

a slower than normal heart rate use of certain drugs used to treat abnormal heart rhythms

arrhythmias

6/25/20146/25/2014 FDA warns of rare but FDA warns of rare but

serious hypersensitivity serious hypersensitivity reactions with certain reactions with certain

over-the-counter topical over-the-counter topical acne productsacne products

The U.S. Food and Drug Administration (FDA) is warning that certain over-the-counter (OTC) topical acne products can cause rare but serious and potentially life-threatening allergic reactions or severe irritation.

The hypersensitivity reactions may occur within minutes to a day or longer after product use.

The OTC topical acne products of concern are marketed under various brand names such as:

Proactiv Neutrogena MaxClarity Oxy Ambi Aveeno Clean & Clear

They are available as gels, lotions, face washes, solutions, cleansing pads, toners, face scrubs, and other products.

Anticholinergic DrugsAnticholinergic Drugs

Toxidrome mneumonic Blind as a bat Dry as a bone Mad as a hatter Hot as a hare Red as a beet

Counseling pointsCounseling points Blind as a bat –

blurry vision dilated pupils caution with driving recommend sunglasses

Dry as a bone decreased saliva increased risk of cavities recommend dental exams

Mad as a hatter confusion memory loss

Counseling pointsCounseling points

Hot as a hare Red as a beet

Both are associated with heat intolerance

Counsel about heat precautions

Anticholinergics - usesAnticholinergics - uses

GI dicyclomine hyoscyamine

Overactive Bladder oxybutynin tolterodine darefenacin solefenacin

Anticholinergics - usesAnticholinergics - uses

Excessive salivation glycopyrrolate atropine scopolamine

Antipsychotic induced EPS benztropine trihexyphenidyl

Anticholinergic DrugsAnticholinergic Drugs

A drug interaction of note

All solid oral dosage forms of potassium chloride are contraindicated in any patient in whom there is structural, pathological (e.g., diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

Prepare an aqueous (water) suspension as follows: Place the whole tablet(s) in approximately one-half glass of water (4

fluid ounces). Allow approximately 2 minutes for the tablet(s) to disintegrate. Stir for about half a minute after the tablet(s) has disintegrated. Swirl the suspension and consume the entire contents of the glass

immediately by drinking or by the use of a straw. Add another one fluid ounce of water, swirl, and consume

immediately. Then, add an additional one fluid ounce of water, swirl, and

consume immediately.

Other agents with Other agents with potential for heat potential for heat intoleranceintolerance

Amphetamines Pseudoephedrine Phenylepherine Zonisamide Topiramate

Other Side Effects with Other Side Effects with TopiramateTopiramate

Taste disturbance Confusion Word-finding difficulties Loss of appetite Visual disturbance

Lotrisone®Lotrisone®

Antifungal/Corticosteroid Often for “jock itch” or diaper rash Skin thinning Functional “occlusive dressing” Systemic side effects “Addictive”

Glucocorticoids - Glucocorticoids - SystemicSystemic

Increased blood glucose HPA axis suppression Decreased bone mineral density Skin thinning Withdrawal Glaucoma

GlaucomaGlaucoma

Or increased intraocular pressure Most common with ophthalmic dosing

- use special care after LASIK Also seen with systemic therapy What about inhaled steroids?

Inhaled GlucocorticoidsInhaled Glucocorticoids

Glaucoma or IOP risk Family history OR 2.6 (1.2 - 5.8) High doses and fam hx OR 6.3 (1.0 -

38.6) No association when no fam. Hx Ask about family history of glaucoma

or IOP when prescribing inhaled steroids Mitchell, et al Ophthalmology 1999;106:2301-2306

Report ADR’sReport ADR’s

Larger patient populations Open-ended time frame Not limited to “healthy adults” JCAHO requires an institutional

policy

Check UpdatesCheck Updates Clin-Alert Australian Adverse Drug Reaction

Bulletin http://www.health.gov.au/tga/adr/aadrb.htm

Med-Safe (New Zealand) http://www.medsafe.govt.nz/profs.htm

Dear Doctor letters Institutional newsletter

LactuloseLactuloseA theoretical hazard may exist for patients being treated with lactulose solution who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy. Accumulation of H2 gas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with a non-fermentable solution. Insufflation of CO2 as an additional safeguard may be pursued but is considered to be a redundant measure.

How do you say you’re How do you say you’re sorry?sorry?

KABOOM!

Brooke Tullos Infectious Disease Travis KingMary Wooten Infectious Disease Travis KingBrooke Tullos Infectious Disease Travis KingMary Wooten Infectious Disease Travis King

FDA AlertsFDA Alerts

7/09/20157/09/2015FDA strengthens warning FDA strengthens warning

that non-aspirin that non-aspirin nonsteroidal anti-nonsteroidal anti-

inflammatory drugs inflammatory drugs (NSAIDs) can cause heart (NSAIDs) can cause heart

attacks or strokesattacks or strokes

The U.S. Food and Drug Administration (FDA) is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke.

Based on our comprehensive review of new safety information, the FDA is requiring updates to the drug labels of all prescription NSAIDs.

The FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels.

7/01/20157/01/2015FDA evaluating the FDA evaluating the

potential risks of using potential risks of using codeine cough-and-cold codeine cough-and-cold

medicines in childrenmedicines in children

Documents

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should