From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (2024)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (1)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (2)

ScopeScope

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (3)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (4)

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

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DefinitionsDefinitions

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (6)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (7)

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

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ADE - Adverse Drug ADE - Adverse Drug EventEvent

Includes medical errors

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (9)

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

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Side EffectsSide Effects

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

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Toxic EffectsToxic Effects

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

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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)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (13)

HypersensitivityHypersensitivity

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (14)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (15)

Assessment of ADR’sAssessment of ADR’s

Temporal relationship Dechallenge Rechallenge Confounders

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (16)

Can Influence ADR’sCan Influence ADR’s

Age Weight Race Sex Pregnancy Concomitant diseases Other drugs or food

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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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (18)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (19)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (20)

Important:Important:

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (21)

Types of Drug InteractionsTypes of Drug Interactions

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (22)

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?

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (23)

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

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Influence of same Influence of same physiological systemphysiological system

Warfarin and NSAIDS Aminoglycosides and

neuromuscular blockers Beta blockers, digoxin, verapamil,

diltiazem Multiple anti-hypertensives

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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

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Absorption interactionsAbsorption interactions

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

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DistributionDistribution

Protein binding mostly theoretical generally transient warfarin and phenytoin

Tissue binding quinidine and digoxin

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (28)

Drug metabolism - Drug metabolism - inductioninduction

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (29)

Drug metabolism - Drug metabolism - inductioninduction

Be careful with oral contraceptives HRT cyclosporine

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (30)

Drug metabolism - Drug metabolism - inhibitioninhibition

Inhibitors azole antifungals

ketoconazole itraconazole

macrolide antibiotic erythromycin clarithromycin

cimetidine

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (31)

Drug metabolism - Drug metabolism - inhibitioninhibition

More inhibitors SSRI’s

fluvoxamine paroxetine fluoxetine

nefazodone fluoroquinolones amiodarone

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (32)

Grapefruit JuiceGrapefruit Juice

Caused by furanocoumarin fractions

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

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Predicting Grapefruit Predicting Grapefruit Juice InteractionsJuice Interactions

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

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

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (36)

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

Lower cholesterol Inhibit rate limiting reaction in

mevalonate pathway Other mevalonic acid products

dilochol (liver, retina) ubiquinone (muscles)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (37)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (38)

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”

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (39)

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

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

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

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (41)

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

Concerns unexplained muscle pain accident hospitalization?

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (42)

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

LimitationsLimitations

Posted:06/08/2011

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (43)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (44)

SimvastatinSimvastatin

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

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SimvastatinSimvastatin

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

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SimvastatinSimvastatin

10 mg/day Diltiazem Verapamil

20 mg/day Amiodarone Amlodipine Ranolazine

Grapefruit juice Avoid > 1 quart/day

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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

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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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (49)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (50)

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

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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?

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (52)

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

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TetracyclinesTetracyclines

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

Hypertension) or Psuedotumor Cerebri

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Tetracyclines - Tooth Tetracyclines - Tooth StainingStaining

Tetracycline - during tooth formation

Binds to calcium Cervical third of tooth (gingival

margin) Avoid during pregnancy Avoid in children

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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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (57)

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Minocycline - Tooth Minocycline - Tooth StainingStaining

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

mg/day

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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

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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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (61)

Tetracyclines - BIHTetracyclines - BIH

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)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (62)

Tetracyclines - BIHTetracyclines - BIH

Ask about headaches tinnitis blurred vision double vision

Check for papilledema

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (63)

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

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Levothyroxine Levothyroxine interactionsinteractions

Calcium Iron (including prenatal vitamins or

other vitamin/mineral preps) Soy protein

all decrease absorption separate by at least 2 hours

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (66)

SSRI withdrawalSSRI withdrawal

Disequilibrium dizziness vertigo ataxia swimming or spaced out feeling impaired coordination

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (67)

SSRI withdrawalSSRI withdrawal GI disturbances

nausea vomiting diarrhea anorexia

Flu-like symptoms

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SSRI withdrawalSSRI withdrawal Sensory disturbances

auditory hallucinations paresthesias electrical shock sensations

CNS symptoms agitation confusion headache lethargy

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SSRI withdrawalSSRI withdrawal Sleep disturbances

insomnia nightmares vivid dreams

relapse of depression

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SSRI withdrawal -SSRI withdrawal -most commonmost common

Dizziness Nausea Lethargy Headache

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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

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SSRI - DM interactionSSRI - DM interaction

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

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DextromethorphanDextromethorphan

Cough/cold preps Adjuvant for pain management

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

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Serotonin syndromeSerotonin syndrome

Mental status changes Tremor Restlessness Incoordination Shivering Increased temperature

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Serotonin syndromeSerotonin syndrome

Diaphoresis Hyperreflexia Myoclonus Diarrhea Convulsions Could be fatal

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SSRI - DM interactionSSRI - DM interaction

If needing a cough suppressant use:

Benzonatate Carbetapentane combinations

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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

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SSRI Induced BruxismSSRI Induced Bruxism

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

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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

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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

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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

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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)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (83)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (84)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (85)

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).

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (86)

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)

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (87)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (88)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (89)

Serotonergic Psychiatric Serotonergic Psychiatric MedicationsMedications

SSRIs SNRIs Tricyclics MAOIs

Other: Amoxapine Maprotiline Nefazodone Trazodone Buproprion Buspirone Vilazodone

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (90)

Serotonin Syndrome Serotonin Syndrome SymptomsSymptoms

Tremor Altered mental status Clonus Muscular hypertonicity hyperthermia

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (91)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (92)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (93)

Methylene blueMethylene blue

Monoamine oxidase inhibitor properties

Urgent treatment of: Methemoglobinemia Ifosfamide-induced encephalopathy Cyanide poisoning

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (94)

AlsoAlso

Urinary medications UTA Urogesic blue

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (95)

Antihistamine/Antihistamine/DecongestantDecongestantCombinationsCombinations

Newer antihistamines Less sedation Long duration of activity Good safety profiles

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (96)

Antihistamine/Antihistamine/DecongestantDecongestantCombinationsCombinations Same decongestants (usually

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (97)

Decongestant ProfilesDecongestant Profiles

050

100150

200250300

350400

450500

3.9 4.4 5 7

Claritin D 12Zyrtec DAllegra DClaritin D 24

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (98)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (99)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (100)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (101)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (102)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (103)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (104)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (105)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (106)

Counseling pointsCounseling points

Hot as a hare Red as a beet

Both are associated with heat intolerance

Counsel about heat precautions

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (107)

Anticholinergics - usesAnticholinergics - uses

GI dicyclomine hyoscyamine

Overactive Bladder oxybutynin tolterodine darefenacin solefenacin

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (108)

Anticholinergics - usesAnticholinergics - uses

Excessive salivation glycopyrrolate atropine scopolamine

Antipsychotic induced EPS benztropine trihexyphenidyl

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (109)

Anticholinergic DrugsAnticholinergic Drugs

A drug interaction of note

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (110)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (111)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (112)

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

Amphetamines Pseudoephedrine Phenylepherine Zonisamide Topiramate

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (113)

Other Side Effects with Other Side Effects with TopiramateTopiramate

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (114)

Lotrisone®Lotrisone®

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (115)

Glucocorticoids - Glucocorticoids - SystemicSystemic

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (116)

GlaucomaGlaucoma

Or increased intraocular pressure Most common with ophthalmic dosing

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (117)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (118)

Report ADR’sReport ADR’s

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

policy

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (119)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (120)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (121)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (122)

FDA AlertsFDA Alerts

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (123)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (124)

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.

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (125)

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

From Grapefruit to Glaucoma: Interactions and Side Effects You Should Be Aware Of From Grapefruit to Glaucoma: Interactions and Side Effects You Should - [PPT Powerpoint] (2024)

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