Medications

Table of Contents

• Vitamins

• Prevention

  • Vaccination

  • Smoking cessation

  • Statins

• Population

  • Inpatient

    • Electrolyte repletion

    • Empiric antibiotics

  • OBGYN: Contraception and pregnancy

  • Pediatric dosing

• Cardiovascular

  • Hypertension

  • ACE inhibitors

  • Anticoagulation and antiplatelets

• Obstructive lung disease

• Antiemetics

• Diabetes mellitus type 2

• Topical steroids

• Pain management

• Prescribing Considerations

  • Contraindications: QTc Prolongation

  • Controlled substances

20 Most Commonly Prescribed Medications

• Pain control: Acetaminophen, ibuprofen, gabapentin, acetaminophen-hydrocodone

• Anti-hypertensive/cardiovascular agents

  • ACE/ARB: Lisinopril/Losartan

  • Beta-blocker: Metoprolol

  • Calcium channel blocker: Amlodipine

  • Diuretics: Hydrochlorothiazide, furosemide

• Statins: Atorvastatin, simvastatin

• Endocrine agents: Metformin, levothyroxine, ergocalciferol (vitamin D2)

• Health maintenance: Aspirin, multivitamin, omega-3 polyunsaturated fatty acid

• Other: Albuterol, omeprazole

Vitamin Deficiencies

Treatment

• Cholecalciferol

  • Pediatric

    • Breast-fed infants age < 6 months: 400 IU qd

    • Asthma: 400 IU qd

    • Rickets: Severe vitamin D deficiency in children, rare in developed nations. Treatment regimen includes 50,000 IU vitamin D3 once weekly x 6 weeks followed by maintenance therapy of 400-1000 IU qd to maintain serum vitamin D levels > 30 ng/ml.

  • Patients with risk factors for vitamin D deficiency: Start 800 IU qd and supplement to 25(OH)D > 30 ng/ml (may require 1500-2000 IU qd)

    • Primary hyperparathyroidism, malabsorptive syndromes including previous bariatric surgery

    • Maintenance medications that interfere with vitamin D synthesis (anticonvulsants, antifungals, antiretrovirals)

  • Patients with multiple sclerosis or at risk of developing multiple sclerosis: 800 IU qd

  • Geriatric fall and fracture prevention (controversial - see below)

    • Age > 65 years: 600 IU qd to prevent falls in community dwelling adults

    • Age > 71 years: 800 IU qd for prevention/treatment of osteoporosis

• Calcitriol: Chronic liver or kidney disease

Vitamin D Resources

• Based on moderate to high quality of evidence, Cochrane systematic reviews showed that there were some benefits from vitamin D supplementation for pregnant women and asthma patients and no benefits for preventing fractures.

• Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline

• A Review on Vitamin D Deficiency Treatment in Pediatric Patients, J Pediatr Pharmacol Ther.

Folate (Vitamin B9)

Deficiency: Insufficient intake, alcoholism, pregnancy/rapid cellular proliferation, cirrhosis, malabsorption, bariatric surgery, thiamin deficiency

Vitamin B12

Resources: https://www.aafp.org/afp/2003/0301/p979.html#afp20030301p979-b3, https://www.aafp.org/afp/2010/0401/p887.html, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725715/, https://pubmed.ncbi.nlm.nih.gov/8154512/, https://www.clinicaladvisor.com/home/features/advisor-forum/causes-of-elevated-methylmalonic-acid/

Deficiency etiologies: Insufficient intake, Celiac disease, pernicious anemia, chronic pancreatitis, malabsorption, bariatric surgery)

Pernicious anemia: https://pubmed.ncbi.nlm.nih.gov/26918709/

• Intrinsic factor antibodies → impaired B12 absorption → megaloblastic anemia characterized by hypersegmented neutrophils

• https://www.youtube.com/watch?v=J8UphjNJljo&ab_channel=HackDentistry

 CDC Vaccination Recommendations

For complete recommendations, download the following PDFs

• Vaccination Ages 0-18 Years

• Vaccination Ages 18+ Years

Vaccination Recommendations for Children

Vaccination Recommendations for Adults

Smoking Cessation Regimens

General Information

• One pack = 20 cigarettes

• Nicotine via inhalation varies widely per subject

  • Approximately 1-2 mg per cigarette (20 to 40 mg/day for 1 pack/day smokers)

  • Second-generation e-cigarettes fluid contains approximately 22 mg/mL

• All forms of nicotine replacement therapy increase chances of successful quitting by 50 to 70%

Medications

Varenicline (Chantix):

• American Thoracic Society 2020 Practice Guidelines

  • Recommended over bupropion and nicotine replacement therapy even in patients with disorder, depression, anxiety, schizophrenia, and/or bipolar disorder

  • Begin treatment rather than waiting until patients are ready to stop tobacco use (strong recommendation, moderate certainty)

  • Recommend treatment for longer than standard duration of 6-12 weeks

• Regimen (12 weeks total)

  • Days 1 to 3: 0.5 mg qd

  • Days 4 to 7: 0.5 mg BID

  • Weeks 2-12: Quit smoking and start 1 mg BID

• Combination with nicotine replacement therapy (NRT)

  • Traditionally recommended against combination with NRT

  • Per American Thoracic Society 2020 guidelines, there is a conditional recommendation with low certainty to combine with NRT

• Contraindications and adverse effects

  • FDA boxed warning: May cause serious neuropsychiatric symptoms in patients, including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide; patient should be monitored closely

  • May result in headache, nausea (dose related), insomnia, abnormal dreams, flatulence

  • May increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease

  • Pregnancy category C

• Retail price: Up to $541/month

Bupropion XL (Wellbutrin)

• Regimen

  • Days 1-3: 150 mg

  • Days 4 to 7: 300 mg qd

  • Week two: Stop smoking and start nicotine replacement therapy (see below)

• May combine with nicotine replacement therapy

• Adverse effects

  • Contraindications

    • History of seizure disorder, eating disorder

    • MAO use (e.g. selegiline) within previous 14 days

  • FDA boxed warning: May increase suicidality in patients with depression

  • May result in insomnia, dry mouth

  • Pregnancy category C

• Retail price: As low as $12/month with GoodRx Coupon

Nicotine Replacement Therapy

Nicotine patch (transdermal): Start on quit date and combine with PRN nicotine replacement

• > 10 cigarettes/day: 21 mg/day patch x 6 weeks, 14 mg/day patch x 6 weeks, 7 mg/day patch until ready to stop

• ≤ 10 cigarettes/day: 14 mg/day patch x 6 weeks, 7 mg/day patch until ready to stop

PRN nicotine therapy

• Dosage for gum and lozenge based on time of first cigarette after awakening

  • < 30 minutes: 4 mg/unit x 6 weeks, 2 mg/unit until ready to stop

  • > 30 minutes: 2 mg/unit until ready to stop

• Gum

  • Common flavors include mint, cinnamon, and mixed fruit

  • Chew gum until nicotine taste appears and then hold gum against buccal mucosa until it disappears

  • Maximum daily dose: 24 pieces

• Lozenges

  • Common flavors include mint and cherry

  • Maximum daily dose: 20 lozenges

• For patients using patch, total nicotine intake with PRN therapy should not exceed amount received via smoking (e.g. 1 pack/day smoker previously receiving up to 40 mg/day via smoking on 21 mg/day patch should try not to use more than 5 pieces of 4 mg/piece gum per day)

Counseling and Alternative Therapies

• Exercise, acupuncture, hypnotherapy are ineffective for smoking cessation

• Address behavior change, especially activities associated with smoking

• Counsel patient about nicotine withdrawal symptoms, depression, and weight gain

• Follow-up shortly before quit date

Resources

• Initiating Pharmacologic Treatment in Tobacco-Dependent Adults: An Official American Thoracic Society Clinical Practice Guideline

• Promoting Smoking Cessation (AFP Journal)

Statin Therapy

• 2019 ACA/AHA Guidelines

• Curbsiders 2020 Review

• Discontinuing statins in the elderly: There may be marginal benefit for ages 70-85 years and harms may outweigh risks in patients age 85 years or olders

2013 Guidelines

Age ≥ 40 years with

• No risk factor and ASCVD

  • < 7.5% → No statin

  • ≥ 7.5% → Moderate intensity statin

• Diabetes mellitus

  • < 7.5% → Moderate intensity statin

  • ≥ 7.5% → High intensity statin

• Atherosclerotic disease with age

  • > 75 years → Moderate intensity statin

  • ≤ 75 years → High intensity statin

• LDL ≥ 190 → High intensity statin

Notes

• Atypical coverage for (Mycoplasma, Legionella) can be achieved with azithromycin, a fluoroquinolone, or doxycycline

• Ciprofloxacin is the only oral antibiotic with pseudomonas coverage

OBGYN Medications

PDF Reference Guides

• CDC Contraception Guidelines

• Patient Education Chart

• Quick Start Algorithm

Oral Contraception Options

Prophylaxis in Pregnancy

Aspirin for Preeclampsia

History of previous preeclampsia, chronic HTN, DM, renal disease, or systemic lupus erythematosus with antiphospholipid syndrome presents to establish OB care. No complications at present. Elevated BP on exam.

• Start aspirin 81 mg daily during first trimester

• Consider higher dose aspirin (162 mg daily) as per evidence

Makena for History of Preterm Delivery

History of previous spontaneous singleton preterm birth presents at <16 WGA.

• Start Makena 250 mg weekly injections at 16 WGA; continue until 37 WGA

• Cervix < 2.5cm on U/S exam

  • Perform serial cervical U/S measurements until 24 WGA

  • Administer vaginal progesterone suppository 200 mg daily

Rho D Immune Globulin

• Reduces risk of alloimmunization in RhD negative women with an RhD positive fetus to 0.2%

• Risk for alloimmunization is low in the 1st trimester, but Rho(D) immune globulin 50 mcg should be offered to women with a threatened early spontaneous abortion

• Indications for administration of Rho(D) immune globulin 300 mcg include

  • At 28 WGA and again within 72 hours of delivery if the infant is Rh positive

  • After events that increase risk of fetal-to-maternal transfusion, e.g.

    • Procedures including amniocentesis, chorionic villus sampling, external cephalic version

    • Abdominal trauma or bleeding in the 2nd or 3rd trimesters

Intrapartum PPx and Tx

Group B Strep

Prophylaxis criteria: Expected vaginal delivery (not required for planned C-section) and at least one of the following

• Positive GBS swab (NAAT) and/or culture confirmed UTI at any point during pregnancy

• Preterm delivery with unknown GBS status; swab is obtained at presentation and therapy is continued pending results

• Term delivery with ROM lasting ≥18 hours

• Maternal fever (≥38.0ºC) at any point during labor

Prophylaxis options

• No PCN allergy: PCN-G 5 million units at presentation and then 2.5 million units q4h until delivery

• PCN allergy (not anaphylaxis): Cefazolin 2 g at presentation and then 1 g every 8 hours until delivery

• PCN and cephalosporin allergies:

  • If susceptible to clindamycin, administer 900 mg every 8 hours until delivery

  • Clindamycin resistant: Vancomycin 2g at presentation and then 1 g q12h until delivery

Pediatric Dosing

Maintenance Fluid

• Weight < 10 kg: 4 mL/kg per hour

• Weight 10 to 20 kg: 40 mL/hr + 2 mL/kg/hr(weight - 10 kg)

• Weight 20 to 80 kg: 40 mL/hr + 20 mL/hr + 1 mL/kg/hr(weight - 20 kg)

“Start 4 mL/hr for the first 10 kg, then 2 mL/hr for the second 10 kg, then 1 mL/hr for each kg after that…”

Antipyretics

 Hypertension Management per JNC 8

Thiazide Diuretics: Additional Information

• Contraindicated if GFR < 30 (exception = metolazone)

• Renal effects

  • Decrease excretion of

    • Calcium → reduced bone mineralization

    • Uric acid → increased gout

    • Lithium → increased toxicity

  • Increase potassium and magnesium excretion

• Agents

  • HCTZ 12.5 and 25 mg daily produce similar decrease in BP

  • Chlorthalidone supported by ALLHAT and SPRINT trials

Secondary Hypertension

Common Etiologies

• Potential contributing factors

  • Diet: Sodium

  • Substances: Caffeine, nicotine, alcohol, cocaine

  • OTC medications: NSAIDs, herbal supplements

  • Prescriptions: OCPs, steroids, EPO

• Hyperaldosteronism

  • Most common pathophysiology

  • May be associated with hypoglycemia

  • Diagnose with aldosterone:renin ratio

Additional Considerations

• Pediatric

  • Coarctation of the aorta: Obtain echocardiogram

  • Renal parenchymal disease: Obtain BMP, U/A, renal ultrasound

• Adult

  • Obstructive sleep apnea

  • Renal artery stenosis

    • Risk factors: Age > 50 years, atherosclerotic disease, fibromuscular disease, smoking

    • May be associated with refractory heart failure, flash pulmonary edema, CKD (ischemic nephropathy)

    • Diagnosis: Renal artery ultrasound with Doppler (or MRA if inconclusive) shows > 60% luminal occlusion

    • Treat cardiovascular risk factors and evaluate for revascularization (e.g. transluminal renal angioplasty +/- stenting)

  • Endocrine: Hyperthyroidism, hypercortisolism, pheochromocytoma

Angiotensin Converting Enzyme (ACE) Inhibitors

Mechanism of Action

↓ angiotensin converting enzyme activity = ↓ conversion of angiotensin I to angiotensin II =

↓ aldosterone production =

• ↓ sodium and fluid retention

• ↓ potassium excretion, possibly leading to increased potassium levels

• ↓ vasoconstriction = ↓ peripheral vascular resistance = ↓ after-load = ↑ cardiac output

Indications for Use

Hypertension

• Not recommended as a first line agent in patients without chronic kidney disease, diabetes, heart failure, or history of STEMI (see below)

• Heuristic: Start as a first line agent in patients who also qualify for statin therapy

• Start lisinopril 10 mg daily

  • Titrate by 10 mg every 4 weeks to maximum dose of 40 mg daily

  • Stop titrating once goal blood pressure is reached

Proteinuric Chronic Kidney Disease (Diabetic and Non-Diabetic)

• Reduces progression of renal disease

• Start ACE in patients with

  • Urine protein excretion > 1000 mg/day

    • Estimate 24-hour urine protein using urine protein:urine creatinine ratio

    • Urine protein/urine creatinine ≈ grams of protein excreted per day

    • 24 hour urine protein calculator

  • Diabetes mellitus type 1 or 2 and urine microalbumin:urine creatinine ratio greater than 30 mg/g/day

• Recommended agent/dose: Enalapril 10 mg daily

Heart Failure with Reduced Ejection Fraction

• Improve symptoms and reduce mortality in patients with LVEF < 40 %

• Start lisinopril 10 mg daily; increase dose by 10 mg every 2 weeks to goal of 40 mg daily

Following ST-Elevation Myocardial Infarction

• Decrease risk of heart failure s/p STEMI

• Start lisinopril 5 mg daily within 24 hours of event provided that patient is stable

  • Increase dose by 10 mg per day while in the hospital

  • Titrate to goal of 40 mg daily; maintain or decrease dose if hypotension develops

• Continue for at least 6 weeks after event

Adverse Effects

• First-dose hypotension

• Bradykinin-mediated

  • Persistent, dry, irritating, and non-productive cough

  • Angioedema

• Fetal injury

Anticoagulation and Antiplatelet Agents

Warfarin Management Tools

INR Goals Summarized

2.0 to 3.0

• DVT and/or PE: Therapy duration varies (see chart)

• Atrial fibrillation: Continue indefinitely

• Valvular disease

  • Rheumatic mitral disease

  • Bioprosthetic or aortic bileaflet valves in patients with

    • No risk factors, i.e. atrial fibrillation, HFrEF, MI, LAE, endocardial damage

    • No history of embolism while appropriately anticoagulated

2.5 to 3.5: Any prosthetic valve not included in the 2.0 to 3.0 category (see above)

Antiplatelet Agents

Clopidogrel Indications

• ACS: Acute dosing varies

• Continuous dosing: 75 mg daily

  • Percutaneous coronary intervention: Dual antiplatelet therapy x 12 months and then continue aspirin only

  • Carotid artery atherosclerosis for patient intolerant of aspirin

  • TIA or ischemic stroke

    • Stenosis of 50% to 69%: 21 days

    • Stenosis of 70% to 99%: 90 days

Obstructive Lung Disease

Antiemetics

Antihistamines

• Dimenhydrinate

  • Indications: Motion sickness, postoperative nausea/vomiting

  • Dose: 50 mg PO every 4 to 6 hours (MDD 400 mg/day)

  • Pregnancy category B

• Meclizine

  • Indications: Motion sickness, vertigo

  • Dose: 25 mg PO every 6 hours (MDD 100 mg/day)

  • Pregnancy category: Unknown

Antimuscarinic: Scopolamine

• Indications: Motion sickness, postoperative nausea/vomiting

• Contraindications: Glaucoma, megacolon, obstructive prostatic hypertrophy, myasthenia gravis

• Dosing

  • Apply 1 patch behind ear daily

  • 10 mg PO every 8 hours (MDD 60 mg/day)

• Pregnancy category: Avoid transdermal patch use in women with preeclampsia

5HT3 Antagonist: Ondansetron

• Indications

  • Generalized N/V

  • N/V due to gastroparesis, pregnancy, vertigo, surgery, chemotherapy, radiation

D2 antagonists

• Metoclopramide

• Prochlorperazine

• Promethazine

Diabetes Mellitus Pharmacotherapy

HbA1c and Corresponding Average Glucose

5.1% (100 mg/dL), 5.8 (120), 6.5 (140), 7.2 (160), 7.9 (180), 8.6 (200)

Non-Insulin Agents

Lower A1c at most by 1% each. High-efficacy unless otherwise noted. See Management of Blood Glucose in Type 2 Diabetes Mellitus for more information.

• Metformin

  • Mechanism: Biguanide that primarily inhibits glucose production by liver

  • Safe if GFR > 30 and Cr 1.5 or less

  • Reduces mortality rates and may reduce risk of cardiovascular events/death

  • Promotes weight loss as compared to thiazolidinediones and sulfonylureas

  • Continue even if patient is started on insulin

• Weight loss and decreased cardiovascular morbidity/mortality

  • SGLT-2 inhibitors: Flozins, e.g. empagliflozin

    • Intermediate efficacy

    • Contraindication: eGFR < 50

  • GLP-1 receptor agonists: Glutides, e.g. liraglutide

    • Mechanism: Stimulate insulin release and inhibit glucagon release

    • Injection, not oral

    • Black box warning: Risk of thyroid C-cell tumors

• Weight neutral: DPP-4 inhibitors: Gliptins, e.g. sitagliptin

  • Mechanism: DPP-4 inhibitors GLP-1 (inhibiting the inhibiting enzyme stimulates insulin release and inhibits glucagon release)

  • Intermediate efficacy

• Weight gain: Low cost medications

  • Thiazolidinediones

    • Mechanism: Improve peripheral insulin sensitivity

    • Glitazones, e.g. pioglitazone

    • High efficacy, low risk for hypoglycemia

    • Pioglitazone reduces non-fatal acute MI, stroke, and all-cause mortality

    • Black box warning: Increases fluid retention and may exacerbate heart failure; contraindicated in NYHA classes III and IV

  • Sulfonylurea

    • Mechanism: Stimulate insulin secretion from pancreatic beta cells

    • E.g glipizide and “irides”

    • Risk for hypoglycemia, especially when combined with other agents

Agents shown to reduce major adverse cardiovascular events/mortality

• Metformin

  • Black box warning: Lactic acidosis (~5 cases per 100,000 patients per year)

  • Start 500 mg qd and increased dose by 500 mg increments every 4 weeks until reaching goal of 1,000 mg BID

• Empagliflozin (Jardiance)

  • Counsel patient about increased risk for UTIs and pancreatitis.

  • 10 mg once daily; may increase to 25 mg once daily as tolerated

• Liraglutide (Victoza)

  • Start 0.6 mg subQ injections once daily for one week

  • Each week, increase daily dose by 0.6 mg if blood sugar not controlled (i.e. week 1 = 0.6 mg daily, week 2 = 1.2 mg daily, etc.)

  • Maximum dose: 3 mg once daily

Insulin

Insulin Pharmacokinetics

• Basal: Physiologic rate of basal insulin production in a non-diabetic patient = 24 units/hour

  • Glargine: Onset 2 hours, no peak, duration 20-24 hours

  • Detemir: Onset 2 hours, peak 3-9 hours, duration 6-24 hours

• NPH: Onset 2 hours, peak 4-12 hours, duration 12 hours

• Rapid acting analogs

  • Examples: Lispro, aspart

  • Onset 3-15 minutes, peak 45-75 minutes, duration 2-4 hours

Switching Basal Insulin to NPH

• NPH BID dose = [(basal insulin)*0.8]/2

• Example

  • Glargine dose = 20 units daily

  • NPH dose = [(20 units)*0.8]/2 = 8 units BID

Rapid Acting Insulin Calculations

• Sensitivity

  • Default: 1 unit insulin = ↓ 40 mg/dL blood glucose. Example: Fingerstick glucose (FSG) 280 mg/dL → 2 units lispro administered → 200 mg/dL after 4 hours.

  • Individual patient sensitivity is calculated based on response (see example below):

    • FSG 280 mg/dL → 2 units rapid acting analog → 240 mg/dL after 4 hours

    • FSG decrease = 280 mg/dL - 240 mg/dL = 40 mg/dL

    • Sensitivity = (40 mg/dL)/(2 units rapid acting analog) = 20

• Insulin:Carb Ratio

  • Default = 1:10

  • Calculated = sensitivity/4

  • Example: Sensitivity = 20, therefore insulin:carb = 20/4 = 1:5

• Rapid acting insulin pre-meal dose = (expected mealtime carbohydrate)/(insulin:carb ratio)

  • 1 piece of bread = 15g and patient plans to eat 4 pieces of toast = 60g carbohydrate

  • Insulin:carb = 1:5

  • 60g carbohydrate/5 = 12 units rapid acting insulin

Topical Steroids

Overview

• Used for multiple inflammatory conditions

• Potency

  • Ranges from group 7 (least potent) to group 1 (most potent)

  • Important when considering percent absorption by body region, e.g.

    • 30% eyelids and genitals

    • 7% face

    • 4% axillae

    • 1% forearms

    • 0.1% palms

    • 0.05% soles

• Agent, frequency of use, and amount included in an initial prescription will vary based on condition and patient

  • The chart below is a general guide for starting treatment

  • Starting amount prescribed to children should be half the adult volume

• Duration

  • Generally, recommend use for 2 to 3 weeks and then discontinuing for two weeks before restarting

  • Steroids not be used for more than 4 weeks continuously

Pain Management

Chronic Pain

• Differential

  • Common conditions: Headache/migraine, back pain, osteoarthritis, fibromyalgia

  • Consider: Neuropathic pain, malignancy, infection

• Adjuvant treatment (information for patients)

  • Lifestyle modification: Hydration, nutrition, sleep hygiene, low-impact exercise, yoga, smoking cessation

  • Massage, physical therapy, occupational therapy

  • Cognitive behavior therapy

  • Complementary and alternative medicine (e.g. acupuncture)

Opioids

• Safe prescribing

  • Opioid conversion calculator

  • Opioids and organ failure

    • Fentanyl is most appropriate for patients with ESRD

    • Methadone should not be used in patients with liver failure

  • Opioids for chronic pain

    • Avoid in general and only start for pain refractory to all reasonable non-opioid analgesic strategies

    • Starting therapy: Continue all non-opioid analgesic therapies, set reasonable treatment goals, and sign pain contract

    • If possible, limit dosing to ≤ 50 oral morphine equivalents per day

    • Prescribe naloxone intranasal 4 mg PRN respiratory depression

    • See patient every month during the first year and perform urine drug screening at each visit

    • After 1 year, see patient every 3 months and perform random urine drug screening at 50% of visits (e.g. per coin-flip)

  • Example regimens

    • Tramadol 50 mg (OME conversion factor = 0.1): 50 mg q8h = 15 OME/day

    • Hydrocodone-acetaminophen 5-325 mg (Norco, Vicodin): 1 tablet q6h = 20 OME/day

    • Oxycodone-acetaminophen 5-325 mg (Percocet): 1 tablet q6h = 30 OME/day

• Decreasing or discontinuing opioids

  • Reasons

    • Patient centered: No significant analgesia despite dose increases, lack of functional improvement, dependency or adverse effects impacting quality of life

    • Health risks (e.g. sleep apnea, chronic pulmonary disease, prolonged QT interval)

    • Dangerous co-prescribing (e.g. benzodiazepines, muscle relaxants, other sedatives)

    • Prescribing > 90 oral morphine equivalents per day

  • Tapering process

    • BRAVO framework: Broaching the subject, risk-benefit calculation, addiction, velocity and validation, other strategies

    • Decrease original dose by 10% every 2 weeks while maintaining original dosing schedule as long as possible

    • Advise patients that body pain will worsen with each dose decrease and then return to baseline

    • Add adjuvant pain control (see chart above) and nonpharmacologic methods (see above)

  • Withdrawal symptom treatment

    • Diarrhea: Loperamide 4 mg q6h PRN for diarrhea

    • Pain/myalgia: Naproxen 500 mg q12h, acetaminophen 650 mg q4h PRN

    • Depression/irritability: Trazodone 50 mg at bedtime, MDD 150 mg (may not improve insomnia)

    • Anxiety: Hydroxyzine 25 mg q8h PRN

• Opioid withdrawal

QTc-Prolongation

QTc Calculation: Put away your calipers and find EKG’s calculated value. For reference…

• QTc = QT/RR

• RR = square root of the difference between R waves of any two QRS complexes

Definition and Significance

• Cut-off values may vary

• QTc >450 milliseconds is generally considered prolonged in both males and females

• QTc >500 milliseconds increase risk for torsades de pointes (see below)

The following list includes drug classes commonly associated with QT-prolongation and the most common offending agents within those classes. Not all drugs in a particular class may cause QT-prolongation and many drugs have been omitted because they are not commonly used in practice.

• Anti-arrhythmics

  • Class I, e.g. procainamide

  • Class III, e.g. amiodarone

• Anti-depressants, e.g.

  • SSRIs

    • Greatest risk: Citalopram/escitalopram

    • Lowest risk: Fluoxetine (Prozac) and sertraline (Zoloft)

  • Venlafaxine (Effexor)

  • Amitriptyline

• Anti-psychotics, e.g.

  • Haloperidol

  • Quetiapine (Seroquel)

  • Ziprasidone (Geodon)

• Antibiotics

  • Fluoroquinolones, e.g. levofloxacin, ciprofloxacin, moxifloxacin

  • Macrolides, e.g. clarithromycin, erythromycin

• Antifungals, e.g. ketoconazole, itraconazole

• Other

  • Anti-emetics, e.g. ondansetron

  • Triptans, e.g. sumatriptan

  • Methadone

Further Reading

• National Health Service’s Post Script Extra on QTc Prolongation

• Funk KA, Bostwick JR. A comparison of the risk of QT prolongation among SSRIs. Ann Pharmacother. 2013 Oct;47(10):1330-41. doi:10.1177/1060028013501994.

Controlled Substances

Opioids

For more information, see pain control

Benzodiazepines

General information

• Include benzodiazepine receptor agonists, e.g. zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta)

• Effectively treat generalized/social anxiety, panic disorder, sleep disorders when prescribed at low doses for a short period of time (< 30 days)

  • Choosing wisely: Don’t use benzodiazepines or other sedative-hypnotics in older adults as first choice for insomnia, agitation, or delirium

• Increase in prescriptions and long-term continuation among primary care physicians is potentially concerning

Risks

• May worsen PTSD symptoms

• Risks while driving: Same as BAC between 0.050% and 0.079%

• Increase risk for hip fractures by 1.5 to 2.55 times

• Long term use: Substantial cognitive decline that did not resolve 3 months after discontinuation

• Beers criteria

  • May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care

  • Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium due to increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents (SOR Strong)

  • Benzodiazepine-receptor agonists

    • Adverse events are similar to those of benzodiazepines in older adults

    • Avoid chronic use, i.e. > 90 days (SOR Strong)

Agents with Primary Care Prescribing Suggestions

Use

• Anxiety: Benzodiazepines are NOT first line (SSRIs, SNRIs are)

• Insomnia: Effect diminishes after a few weeks

• Seizure disorder: Should be managed by neurology

Start taper for any patient taking daily benzodiazepines for > 1 month, especially:

• Age > 65 years

• If also taking opioids or amphetamines

• In patients with history of a substance abuse, cognitive disorder, and/or TBI

Codes

• Code A - Panic Disorder

• Code B - Behavior/Attention Deficit

• Code C - Chronic Debilitation/Neurological Disorder/Seizures etc

• Code D - Chronic pain/Incurable

• Code E - Narcolepsy

• Code F - Hormone Deficiency/Metastatic Breast Cancer