Controlled Substances Update
July 19, 2105
Richard L. Ogletree, Jr., PharmD
Co-ordinator, Drug Information and
Investigational Drugs
University of Mississippi Medical Center

Faculty Disclaimer
Nothing to disclose in regards to commercial support.

Part 2610
Chapter 2: CME Requirements
Rule 2.1
Basic Requirement
Every Mississippi licensee must earn or receive not less than forty (40) hours of
Category 1 continuing medical education in a two-year cycle as a condition precedent to renewing his or her license for the next fiscal year.

Part 2610
Chapter 2: CME Requirements
Rule 2.1
Basic Requirement
For every Mississippi licensee with an active
DEA certificate, five hours must be related to the prescribing of medications with an emphasis on controlled substances.

•
•
•
•
Purpose
To enhance patient care by providing prescription monitoring information to assure legitimate use of controlled substances
To help curtail misuse and abuse of controlled substances
To assist in combating illegal trade
To enable access to prescription information by authorized individuals


Reduce prescription drug abuse and diversion

Electronically collect, monitor, and analyze prescribing and dispensing data

PMPs do not interfere with the appropriate medical use of controlled substances

50 states with legislation enacted

41 states with an operational PMP


ED providers checked 179 patients

PMP changed Rx 41%


61% decreased Rx
39% increased Rx
Baehren DF et al: A statewide prescription monitoring program affects emergency department prescribing.
56:24-26.
Ann Emerg Med 2010

American College of Emergency Physicians

What prevents you from checking the PMP on every patient for whom you prescribe controlled substances?
Perrone et al: Prescribing practices, knowledge and use of prescription monitoring programs by a national samp of clinicians, 2012

How often are you using the
PMP?

What would you like to change about your state's
Prescription Drug Monitoring Program?


•
•
•
•
•
Who is Provided Access?
Law Enforcement for drug investigations (open investigations and sometimes court orders are required)
Licensing and Regulatory Boards for investigating health care professionals who prescribe or dispense prescription controlled substances
State Medicaid Programs for Medicaid member or provider reviews
State medical examiners or coroners for cause of death investigations
Research organizations that may be provided deidentified data for analysis and research

What Drugs are Monitored?
Schedules
Collected
Schedule II
States
PA
Schedules II-III CT
Schedules II-IV
AZ, CA, FL, IA, KS, ME, MN, NV, NJ,
NM, OR, RI, SC, SD, VT, VA, WI, WV,
WY
Number
1
1
17
Schedules II-V
AK, AL, AR, CO, DE, GA, Guam, HI, ID,
IL, IN, KY, LA, MA, MI, MS, NY, NC,
ND, MD, MT, OH, OK, TN, TX, UT, WA
28
To be determined NE 1

Who Administers PMPs?
Agency Type
Consumer Protection
Substance Abuse
Law Enforcement
Professional Licensing
Departments of Health
Boards of Pharmacy
TOTAL
7
15
18
49
3
7
Number
1

Mississippi’s PMP




Reporting for Schedule II – V, including carisoprodol, tramadol, and butalbital
Pharmacies and other dispensers must provide such reporting
Authorized users include: prescribers, pharmacists, law enforcement officers, licensure board, Medicaid, grand jury, judges, probation, or parole officers https://mississippi.pmpaware.net/login

Preliminary Analyses of PMPs

Can PMPs really help limit opioid abuse?

Goal: to facilitate informed prescribing

Limited data for effectiveness

One study observed a 4.9% per quarter increase in opioid treatment admissions in states w/o PMP

Barriers identified for physicians and other health care providers participating

What would be the ideal PMP?

•
Problem: people abusing medications may not stay in one state
•
Result: the state PMP may not be a complete picture
•
Possible solution: PMP Interconnect
–
Hub created through NABP that shares information within member
states
Physicians and pharmacists log into their own state PMP and check boxes for information through other states

Prescription Monitoring Program



Sign up: https://mississippi.pmpaware.net/login
Can not use an email address that anyone else is able to access
Nurse Practitioners must use the system themselves and may not delegate this responsibility to anyone else

Regulations

DEA Regulations –
Controlled Substances
A prescription for a controlled substance must be dated and signed on the date when issued. The prescription must include the patient’s full name and address, and the practitioner’s full name, address, and DEA registration number.

DEA Regulations –
Controlled Substances







The prescription must also include:
Drug name
Strength
Dosage form
Quantity prescribed
Directions for use
Number of refills authorized (if any)

DEA Regulations –
Controlled Substances
A prescription must be written in ink or indelible pencil or typewritten and must be manually signed by the practitioner on the date when issued. An individual (i.e., secretary or nurse) may be designated by the practitioner to prepare prescriptions for the practitioner’s signature. The practitioner is responsible for ensuring the prescription conforms to all requirements of the law and regulations, both federal and state.

MSBN Regulations –
Controlled Substances




Do not let anybody else sign Rx for you
Do not pre-sign Rx blanks
Cannot mechanically or photostatically reproduced signature or controlled substance prescribed
No e-mailed prescriptions

Regulations –
Controlled Substances

Rx for controlled substances expire 6 months from the date written

Regulations –
Controlled Substances

No more than one (1) controlled substance shall be issued on a single prescription blank.

Regulations –
All Prescriptions




Preprinted or clearly printed name of prescriber
Multiple preprinted prescribers – indicate which one
Multiple meds – clear refills for each
No fax for nalbuphine, carisoprodol, butalbital compounds, or tramadol
(MSBML)

Repeat
No fax for tramadol, carisoprodol, butalbital compounds, or nalbuphine!
(MSBML)

electronic transmission of controlled substance prescription data is limited to computer to facsimile (fax) transmissions or traditional fax to fax transmissions.
Requirements for fax prescription orders and systems utilized for faxing prescriptions are as follows

The prescription order shall contain the date, time, telephone number and location of the transmitting device.
Prescription blanks utilized in this manner shall bear a pre-printed heading that indicates the blank is a “Fax
Prescription Form.”
Fax prescription orders must contain a manual or authenticated electronic/digital signature of the prescriber.

Diet Medications
It is unlawful to prescribe, dispense or administer any amphetamine or amphetamine-like anorectic and/or central nervous system stimulant classified as Schedule II for the exclusive treatment of obesity, weight control, or weight loss.

Diet Medications
As to the administration, dispensation or prescription of controlled substance anorectics in Schedules III, IV and V, use of said medications in the treatment of obesity or weight loss should be done with caution.

Diet Medications
Medications for the purpose of weight loss in the treatment of obesity should be used only as an adjunct to a regimen of weight reduction based on caloric restriction, provided, that all of the following conditions are met:

Diet Medications
Review of records indicate a good faith effort to lose weight has been made utilizing: a regimen of weight reduction based on caloric restriction, nutritional counseling, behavior modification, and exercise, without the utilization of controlled substances, and that said treatment has been ineffective.

Diet Medications
Before initiating treatment utilizing a
Schedules III, IV or V controlled substance, the prescriber
 obtains a thorough history
 performs a thorough physical examination of the patient

Diet Medications
 rules out the existence of any recognized contraindications to the use of the controlled substance to be utilized. “Recognized contraindication” means any contraindication to the use of a drug which is listed in the United
States Food and Drug Administration
(hereinafter, “F.D.A.”) approved labeling for the drug.

Contraindications





Advanced arteriosclerosis
Cardiovascular disease
Moderate to severe HTN
Hyperthyroidism
Allergy to this or other sympathomimetic amines

More Contraindications



Agitated states
Hx of drug abuse
MAO inhibitors within 14 days

Diet Medications
The prescriber shall not utilize any
Schedules III, IV or V controlled substance when he or she knows or has reason to believe that a recognized contraindication to its use exists.

Diet Medications
The prescriber shall not utilize any
Schedules III, IV or V controlled substance in the treatment of a patient whom he or she knows or should know is pregnant.

Diet Medications
As to those controlled substances in
Schedules III, IV or V which are classified as amphetamine or amphetamine-like anorectics and/or central nervous system stimulants, hereinafter referred to as “stimulant”…

Diet Medications the prescriber shall not initiate or shall discontinue utilizing said controlled substance stimulant immediately upon ascertaining or having reason to believe:

Diet Medications

A. That the patient has failed to lose weight while under treatment with said stimulant over a period of thirty (30) days, which determination shall be made by weighing the patient at least every thirtieth (30th) day …

Diet Medications
 except that a patient who has never before received treatment for obesity utilizing a stimulant, and who fails to lose weight during his or her first such treatment attempt may be treated with a different controlled substance for an additional thirty (30) days.

Diet Medications

B. That the patient has developed tolerance (a decreasing contribution of the drug toward further weight loss) to the anorectic effects of said stimulant being utilized.

Diet Medications


C. That the patient has a history of or shows a propensity for alcohol or drug abuse.
D. That the patient has consumed or disposed of any controlled substance other than in strict compliance with the treating physician's directions.

Diet Medications

In addition to the above the prescriber shall not issue a prescription or dispense a stimulant for any greater than a thirty (30) day supply;


Diet Medications
And a patient’s use of stimulants, whether by dispensation or prescription shall be limited to no more than six (6) thirty (30) day supplies during any twelve (12) month period of time.

No longer valid – As of November 2012, this regulation has been deleted.

Diet Medications
And further, before subsequent new prescriptions can be issued the patient shall receive a thorough reevaluation of the effectiveness of the medication, including a physical examination to document any potential harmful side effects.

Diet Medications
A prescriber shall not utilize a Schedules
III, IV or V controlled substance or legend drug for purposes of weight loss unless it has an FDA approved indication for this purpose and then only in accordance with all of the above enumerated conditions.

Diet Medications
A prescriber shall not utilize a Schedules
III, IV or V controlled substance or legend drug for purposes of weight loss unless it has an FDA approved indication for this purpose and then only in accordance with all of the above enumerated conditions.

Diet Medications
The purpose of this rule is to prohibit the use of such drugs as diuretics and thyroid medications for the sole purpose of weight loss.

Other considerations



Expiration of rx


Controlled 6 months
Non-controlled – 1 year
Copies (between pharmacies)

Only non-controlled
Pseudoephedrine – RX only in MS

Dispense as Written


Pay attention to the Rx pad
Medicaid has different requirements hand write “ Brand Medically
Necessary”

Dispense as Written


Pay attention to the Rx pad
Medicaid has different requirements hand write “ Brand Medically
Necessary”

Dispense as Written
Consider DAW 1



Coumadin
Antiepileptics
Thyroid medicines

FDA Approval




Presence on the market does not equate to FDA approval
1938 – safety
1962 – efficacy
Many products “grandfathered”

FDA AB Rating


Required for substitution by many chains
Expect telephone calls

No FDA Approval


Midrin
Novahistine DH



Pyridium
Anusol HC
Levsin

FDA Withdrawals


Quinine
Guaifenesin ER




Hydrocodone cough syrups
Codeine products
Morphine
Oxycodone

FDA Approved
Hydrocodone cough syrups



Hycodan

Hydrocodone and homatropine

Adults - one tsp q4-6h prn cough
Tussionex

Adults - one tsp q12h
Hydrocodone with APAP liquid is still available (pain)

FDA Approved
Hydrocodone cough syrups



Hycodan

Hydrocodone and homatropine

Adults - one tsp q4-6h prn cough
Tussionex

Adults - one tsp q12h
Hydrocodone with APAP liquid is still available (pain)

Speaking of Hydrocodone…

a. Authority To Prescribe HCPs as
Schedule II Controlled Substances
In Mississippi Nurse Practitioners and
Physician Assistants can obtain DEA authority to prescribe C II medications.

b. Transmittal Method of HCPs as
Schedule II Controlled Substances
Oral and Facsimile Prescriptions – in general this is not allowed
Triplicate Prescriptions – not required in
Mississippi

c. Quantity and Frequency of Fills and Refills for HCPs as Schedule II
Controlled Substances
Although the CSA prohibits refills of prescriptions for schedule II controlled substances, a practitioner may issue multiple schedule II prescriptions in order to provide up to a 90-day supply of medication in accordance with 21 CFR
1306.12.
Date should be the date actually written
Can utilize a “Do Not Fill Before…“ message

Remember…
• Date should be the date actually written
• Can utilize a “Do Not Fill Before…“ message

Prescriptions
All prescriptions for HCPs must comply with 21 U.S.C. 829 (a) and must be issued in accordance with 21 CFR part 1306 and subpart C of 21 CFR part 1311 as of
October 6, 2014.

Prescriptions
No prescription for HCPs issued on or after October 6, 2014 shall authorize any refills.

Prescriptions
Any prescriptions for HCPs that are issued before October 6, 2014, and authorized for refilling, may be dispensed in accordance with 21 CFR 1306.22
-
1306.23, 1306.25, and 1306.27, if such dispensing occurs before April 8, 2015.

Discontinued Medications



Tylenol with codeine elixir

Write APAP with codeine elixir
Robitussin AC


Write guaifenesin with codeine
Or Cheratussin AC
Mepergan Fortis

Generics are discontinued also

Medications Causing Confusion




Adderall vs Adderall XR
Focalin vs Focalin XR
Metadate ER vs Metadate CD
Ritalin vs Ritalin SR vs Ritalin LA

FDA Safety Alerts –
Zolpidem

Next-day impairment a significant concern, especially with extendedrelease products and in women

Recommended lower dose (women):

Immediate release – 10mg  5mg

Extended release – 12.5mg  6.25mg

FDA Safety Alerts –
Zolpidem



Always use lowest dose possible
Intermezzo already has lower dosage recommendation for women incorporated into FDA labeling
FDA later added language to Ambien CR package insert to warn patients not to drive or engage in activities requiring mental alertness the day after taking the drug.

FDA Safety Alerts –
Eszopiclone



Recent study found 3mg dose can cause impairment of driving skills, memory, and coordination that may last
>11 hours
Recommended decreasing initial dose from 3mg to 1mg.
Applies to both men and women

FDA Safety Alerts – Codeine


[ 7-1-2015 ]
FDA Drug Safety Communication:
FDA evaluating the potential risks of using codeine cough-and-cold medicines in children

FDA Safety Alerts – Codeine

The U.S. Food and Drug Administration (FDA) is investigating the possible risks of using codeinecontaining medicines to treat coughs and colds in children under 18 years because of the potential for serious side effects, including slowed or difficult breathing. We are evaluating all available information and will also consult with external experts by convening an advisory committee to discuss these safety issues. We will communicate our final conclusions when our review is complete.

FDA Safety Alerts – Codeine

Parents and caregivers who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness in their child should stop giving their child codeine and seek medical attention immediately by taking their child to the emergency room or calling 911.

FDA Safety Alerts – Codeine

In April 2015 , the European Medicines Agency
(EMA) announced that codeine must not be used to treat cough and cold in children under
12 years, and that codeine is not recommended in children and adolescents between 12 and 18 years who have breathing problems, including those with asthma and other chronic breathing problems.

Medical Literature

Article: Rubinstein A, Carpenter DM.
Elucidating Risk Factors for Androgen
Deficiency Associated with Daily Opioid
Use. The American Journal of Medicine
[Internet]. 2014 Jul; Available from: http://linkinghub.elsevier.com/retrieve/ pii/S0002934314005956

Medical Literature

Retrospective cohort study


The Kaiser Permanente Northern
California databases (approximately 3.2 million lives served) was used to identify men on stable doses of opioids.
The study included 1585 men.

Medical Literature

Men on long-acting opioids were more likely to be androgen deficient than men on shortacting opioids (57% vs. 35%, P < 0.001; odds ratio [OR] 3.39, 95% CI 2.39–4.77).

Medical Literature


As dose increased, the odds of androgen deficiency increased;
Dose was more strongly associated with androgen deficiency in men on short-acting opioids (OR 1.16, 95% CI 1.09–1.23, for each
10-mg increase in dose) than in men on longacting opioids (OR 1.01, 95% CI 1.01–1.02).

https://video.search.yahoo.com/video/play;_ylt=A2KLqIDXl6tVMmMAvzYsnIlQ;_ylu=X3oDMTBzc2M2MjdyBHNlYwNzcgRzbGsDdmlkBHZ
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FDA Safety Alerts –
Testosterone

Announced in Jan 2014 that FDA is investigating risk of stroke, heart attack, and death in men taking testosterone.


JAMA article showed 30% increase in risk of stroke, heart attack, and death
PLOS article found RR=2.9 for MI in younger patients with pre-existing heart disease

FDA Safety Alerts –
Testosterone



No conclusions at this point
At this point, prescribers urged to weigh risk vs. benefit of therapy
FDA reinforced that currently approved products are only approved for patients with low testosterone and and associated medical disease.

FDA Safety Alerts –
Testosterone


Testosterone products are approved
only for men who have low testosterone levels caused by certain medical conditions
Labels have been updated to clarify the approved uses of these products and include information about a possible increased risk of heart attacks and strokes in patients taking testosterone.

FDA Safety Alerts –
Methylphenidate



FDA warned in Dec 2013 that methylphenidate products may cause priapism in males taking product for
ADHD
Younger patients may not recognize problem or may be too embarrassed to report.
Male patients and caregivers should be taught signs and symptoms of priapism

FDA Safety Alerts –
Methylphenidate


Safety communication discouraged prescribers from switching to Strattera
(atomoxetine) due to fears of priapism, since priapism appears to be more common with this drug.
Unclear whether amphetamines associated with priapism

FDA Safety Alerts –
Methylphenidate


[ 06-24-2015 ]
FDA Drug Safety Communication:
FDA reporting permanent skin color changes associated with use of Daytrana patch
(methylphenidate transdermal system) for treating ADHD

FDA Safety Alerts –
Methylphenidate

The U.S. Food and Drug Administration
(FDA) is warning that permanent loss of skin color may occur with use of the Daytrana patch (methylphenidate transdermal system) for Attention Deficit Hyperactivity Disorder
(ADHD). FDA added a new warning to the drug label to describe this skin condition, which is known as chemical leukoderma.






FDA Safety Alerts –
Methylphenidate
FDA 52 cases April 2006 - December 2014
The time to onset - 2 months to 4 years
All of the patients described a decrease in or loss of skin color.
In most cases, the loss of skin color was limited to the areas around where the patch was rotated.
However, a small number of patients also reported skin color changes on parts of the body where the patch was never applied. In all cases, the decreased skin color was permanent..

New FDA Approved

Belviq

Lorcaserin hydrochloride

Indicated as adjunct to a reduced-calorie diet and increased physical activity for chronic weight management with an initial BMI of:

30 kg/m2 or greater (obese)

27 kg/m2 or greater (overweight) and one weight related comorbidity (e.g.
HTN, DLD, T2DM)

New FDA Approved

Belviq
 one 10 mg tablet PO BID
 evaluate response to therapy by week 12
 if patient has not lost at least 5% baseline body weight, d/c Belviq as continued treatment not likely to be efficacious

New FDA Approved

Belviq

Schedule IV

Warnings






Serotonin syndrome

DDI: triptans, MAOIs, SSRIs, SNRIs dextromethorphan,
TCAs, bupropion, lithium, tramadol, tryptophan, St.
John's wort
Cognitive impairment
Hypoglycemia in T2DM
Priapism
Increase in heart rate
Pregnancy category X

New FDA Approved

Qsymia

Schedule IV


Phentermine and topiramate
For weight management

New FDA Approved

Qsymia
 one capsule 3.75mg/23mg daily for 14 days, then increase to 7.5mg/46mg daily




D/C or escalate dose if 3% weight loss is not achieved after 12 weeks on 7.5mg/46mg
D/C if 5% weight loss is not achieved after 12 weeks on maximum daily dose of 15mg/92mg
D/C 15mg/92mg dose gradually to prevent possible seizure
Do not exceed 7.5mg/46mg with moderate or severe renal impairment or patients with moderate hepatic impairment

New FDA Approved

Qsymia

Contraindications


Pregnancy
Glaucoma



Hyperthyroidism
During or within 14 days following the administration of MAOis
Known hypersensitivity or idiosyncrasy to the sympathomimetic amines

New FDA Approved

Qsymia

Warnings


Increase in heart rate
Suicidal behavior and ideation



Mood disorders
Acute myopia
Oligohydrosis and hyperthermia

New FDA Approved

Qsymia

DDI


MAOis
Oral contraceptives




CNS depressants including alcohol(e.g. barbiturates, benzodiazepines, and sleep medications)
Non-potassium sparing diuretics(e.g. hydrochlorothiazide)
Antiepileptic drugs(e.g. valproic acid)
Carbonic anhydrase inhibitors(e.g. zonisamide, acetazolamide, dichlorphenamide)

New FDA Approved

Fycompa
 perampanel


For seizures (adjunct therapy – partial onset)
One 2 mg tablet daily at bedtime, increased by 2 mg/day increments no more frequently than weekly to a dose of 4 to 8 mg daily

New FDA Approved

Fycompa

Warnings



Psychiatric and behavioral reactions
Suicidal behavior and ideation
Dizziness, gait disturbance, somnolence and fatigue, increased risk of falls


Schedule III
DDIs


Levonorgestrel
Alcohol and other CNS depressants

New FDA Approved

New FDA Approved

Suvorexant

MOA - orexin (hypocretin) receptor antagonist. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wakepromoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

New FDA Approved

Suvorexant

Indication - treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Contraindaction - narcolepsy


New FDA Approved
Suvorexant

Dosage and administration

Use the lowest dose effective for the patient



Recommended dose is 10 mg, no more than once per night taken within 30 minutes of going to bed, with at least 7 hours remaining before the planned time of awakening.
If the 10 mg dose is well tolerated but not effective, the dose can be increased, not to exceed 20 mg once daily.
Time to effect may be delayed if taken with or soon after a meal

New FDA Approved

Suvorexant

Drug interactions

Avoid with strong inhibitors of CYP3A






 ketoconazole itraconazole, posaconazole clarithromycin nefazodone ritonavir, saquinavir





 nelfinavir indinavir boceprevir telaprevir telithromycin conivaptan


New FDA Approved
Suvorexant

Drug interactions
5 mg in subjects receiving moderate CYP3A inhibitors





 amprenavir aprepitant atazanavir ciprofloxacin diltiazem erythromycin




 fluconazole fosamprenavir grapefruit juice, imatinib verapamil
The dose can be increased to 10 mg in these patients if necessary


New FDA Approved
Suvorexant – potential issues




CNS depressant effects and daytime impairment
Abnormal thinking and behavioral changes
Worsening of Depression/Suicidal ideation
Sleep paralysis, hypnagogic/hypnopompic hallucinations, cataplexy-like symptoms


New FDA Approved
Suvorexant

Side effects

Drowsiness – including next day. Caution those using 20 mg against next-day driving


New FDA Approved
Suvorexant

Keep in mind exposure to drug increased in

Females

Obese

A particular problem in obese females – use lower doses

Pharmacology

Pain Pathways

Pharmacology - Opioids

Pharmacology - Opioids

Histamine release

Pharmacology - Opioids

Histamine release - itching

Pharmacology - Opioids


Histamine release - itching
Nausea

Pharmacology - Opioids



Histamine release - itching
Nausea
Analgesia

Pharmacology - Opioids




Histamine release - itching
Nausea
Analgesia
Sedation

Pharmacology - Opioids





Histamine release - itching
Nausea
Analgesia
Sedation
Euphoria

Pharmacology - Opioids






Histamine release - itching
Nausea
Analgesia
Sedation
Euphoria
Respiratory depression

Don’t Forget

Don’t Forget

Constipation

Don’t Forget

Constipation


Stool softener
Stimulant

Side notes

Side notes

NSAIDS

Naproxen vs Naproxen Sodium

Side notes

NSAIDS


Naproxen vs Naproxen Sodium
Naproxen Sodium works faster – better when prn needed


NSAIDS

Ketorolac
Side notes

Side notes

NSAIDS


Ketorolac
Limit to 5 days therapy


NSAIDS

CV safety
Side notes

Side notes

NSAIDS


CV safety
Worst seem to be
 celcoxib
 diclofenac

Side notes

Simvastatin


Max dose = 40 mg
20 mg if on

Amlodipine


Amiodarone
Ranolazine

10 mg if on

Diltiazem

Verapamil

Side notes

Citalopram


Max dose = 40 mg
20 mg over 60 years old

New FDA Approved - Opiates

Nucynta (tapentadol)





Schedule II Controlled Substance
Available IR and ER
Unique MoA - μ-opioid and NE


Additional receptor target an attempt to treat chronic, neuropathic pain
Post-marketing reports of serotonin syndrome with concomitant use of SSRIs and SNRIs
Use with caution in pts with hx of seizures
Initiate 50 mg, 75 mg, or 100 mg q 4-6 hours depending on pain intensity

New FDA Approved - Opiates

Nucynta (tapentadol)

Contraindications



Respiratory depression
Acute or severe bronchial asthma
MAOIs within 14 days

DDI

Alcohol, other opioids, CNS depressants



MAOIs
Serotonergic drugs (e.g. SSRIs and SNRIs)
Anticholinergic agents (e.g. diphenhydramine)

New FDA Approved - Opiates

Zohydro ER (hydrocodone bitartrate)

First extended release hydrocodone product without acetaminophen



Approximately 1:1 conversion with oxycodone per package insert
Not tamper-resistant
Initiate with 10 mg capsule BID, titrated in increments of 10 mg every 3 to 7 days to achieve adequate analgesia


Single 50 mg capsule or total daily dose greater than 80 mg is only for patients tolerant to an opioid of comparable potency
Schedule II

New FDA Approved - Opiates

UPDATE: Zohydro ER with BeadTek




New formulation approved January 30, 2015 with abuse-deterrent properties
Mix of inactive beads, active IR hydrocodone beads and active ER hydrocodone beads
When crushed and dissolved in liquids or solvents, the inactive beads are designed to immediately form a viscous gel
Available: 10, 15, 20, 30, 40, and 50 mg capsules

New FDA Approved - Opiates

Hysingla ER (hydrocodone bitartrate)

First hydrocodone with FDA-approved labeling that describes
abuse-deterrent characteristics

Indicated for the mgmt of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate


Available in 7 dosage strengths: 20, 30, 40, 60, 80, 100, 120 mg
Starting dose for patients who are not opioid tolerant is
Hysingla ER 20 mg tablet orally every 24 hours

Do not abruptly discontinue Hysingla ER

New FDA Approved
Formulations

Quillivant XR

Methyphenidate HCl



For ADHD
First and only extended-release liquid medicine for ADHD
Starting dose is 20 mg ER PO suspension once daily in the morning, titrated weekly in increments of 10 to 20 mg.


Schedule II
Available as 5mg/mL in different quantities:




300 mg/60 mL
600 mg/120 mL
750 mg/150 mL
900 mg/180 mL

New FDA Approved
Formulations

Targiniq ER ( Oxycodone HCl and Naloxone HCl)



Schedule II
For the long-term management of severe pain that requires daily, around-the-clock treatment
BBWs





Addiction, abuse and misuse
Respiratory depression
Accidental ingestion
Neonatal opioid withdrawal syndrome
CYP 3A4 interaction (initiation of 3A4 inhibitors or discontinuation of 3A4 inducers can result in overdose)

New FDA Approved
Formulations

Targiniq (continued)


Contraindications





Significant respiratory depression
Acute or severe bronchial asthma
Known or suspected paralytic ileus or GI obstruction
Moderate to severe hepatic impairment
Hypersensitivity to oxycodone or naloxone
Available in 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20 mg

New FDA Approved
Formulations

Targiniq (continued)


Starting dose for opioid naïve or intolerant patients is 10 mg/5 mg every 12 hours
Conversion from other opioids (per package insert):


Convert total daily dose to the morphine equivalent
Convert to starting dose using the table below

New FDA Approved
Formulations

Subsys
 fentanyl sublingual spray


Not bioequivalent with other fentanyl products
Used for breakthrough cancer pain in those receiving and tolerant to around-the-clock opioid pain medicine

New FDA Approved
Formulations

Subsys

Initial dose is always 100 mcg except in patients already using Actiq

Subsequent titration steps are 200 mcg, 400 mcg, 600 mcg, 800 mcg, 1200 mcg, and 1600 mcg


One dose should be consumed, wait for 30 minutes, if needed ONLY ONE additional dose until at least 4 hours. If inadequate relief with one dose then increase dose to next highest strength
Schedule II

New FDA Approved
Formulations

Suprenza
 phentermine hydrochloride ODT


For weight management

BMI ≥ 30 kg/m 2 or ≥ 27 kg/m 2 with other risk factors
One ODT tablet (strengths are 15 mg, 30 mg, or 37.5 mg) in the morning

New FDA Approved
Formulations

Suprenza

Avoid in evening due to possibility of insomnia



Common side effects include dry mouth, nervousness, constipation, nausea
Rare but serious side effect includes primary pulmonary hypertension
Schedule IV

New FDA Approved
Formulations

Zubsolv
 buprenorphine and naloxone sublingual ODT



For treatment of opioid dependence one or two sublingual tablets once daily (available as 1.4 mg/0.36 mg or 5.7 mg/1.4 mg) in the range of 2.8 mg/0.72 mg to 17.1 mg/4.2 mg for opioid dependence to be adjusted in 1.4 mg/0.36 mg increments
Schedule III

New FDA Approved
Formulations

Xartemis XR

First and only oxycodone and acetaminophen extended release tablet



Not interchangeable with other oxycodone/APAP formulations
For acute severe pain
Two tablets q 12 hours (supplied as 7.5 mg oxycodone/325 mg APAP tablets)


One tablet at a time, don’t pre-wet prior to placing in mouth but should be taken with enough water to allow for immediate swallowing
Schedule II

New FDA Approved
Formulations

Natesto (testosterone) – nasal gel




Schedule III
Two actuations (11mg) in each nostril TID
Contraindications


Men with carcinoma of the breast or prostate cancer
Pregnant or breast feeding women
Adverse effects – increased PSA, headache, rhinorrhea, epistaxis, nasal discomfort, nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, and nasal scab

New FDA Approved
Formulations

Vogelxo (testosterone) – topical gel




Schedule III
BBWs are related to secondary exposure to testosterone
Warnings and precautions:


Monitor for worsening of BPH
Gel is flammable until dry
No claims of benefit over other testosterone gels currently on the market

New FDA Approved
Formulations

Aveed (testosterone undeconate) – injectable that requires less frequent dosing

3 mL (750 mg) IM (only in every 10 weeks thereafter gluteus medius ) at 0, 4, and

BBWs:




Anaphylaxis
Pulmonary oil microembolism (POME)
Must be observed 30 minutes in a healthcare setting after injection to look for anaphylaxis and/or POME
Only available through the Aveed REMS Program

New FDA Approved
Formulations

Evzio (naloxone)



Autoinjector for opioid overdose
Autoinjector with electronic voice instruction system similar to Auvi-Q
0.4 mg / 0.4 mL in each prefilled autoinjector as a onetime dose

New FDA Approved
Formulations

Bunavail (buprenorphine/naloxone)



Schedule III
For opioid addiction
Buccal film

Has better absorption than Suboxone (about half the dose of buprenorphine) and therefore harder to abuse

New FDA Approved
Formulations

Zubsolv

Schedule III

 physicians only buprenorphine and naloxone sublingual ODT


For treatment of opioid dependence one or two sublingual tablets once daily (available as 1.4 mg/0.36 mg or 5.7 mg/1.4 mg) in the range of 2.8 mg/0.72 mg to 17.1 mg/4.2 mg for opioid dependence to be adjusted in 1.4 mg/0.36 mg increments


New FDA Approved
Formulations
Xartemis XR

Schedule II


First and only oxycodone and acetaminophen extended release tablet

Not interchangeable with other oxycodone/APAP formulations
For acute severe pain

Two tablets q 12 hours (supplied as 7.5 mg oxycodone/325 mg APAP tablets)

One tablet at a time, don’t pre-wet prior to placing in mouth but should be taken with enough water to allow for immediate swallowing

New FDA Approved
Formulations

Tuzistra™ XR
(Codeine polistirex and chlorpheniramine polistirex) extended-release oral suspension,
CIII


The lead programme in Vernalis' cough cold pipeline,
Tuzistra™ XR, was approved by the US FDA in April 2015 for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older.

New FDA Approved
Formulations



 pink to reddish pink, cherry-flavored liquid oral suspension containing in 5 ml codeine polistirex, providing 14.7 mg of codeine (equivalent to 20 mg codeine phosphate), and chlorpheniramine polistirex, providing 2.8 mg chlorpheniramine (equivalent to 4 mg chlorpheniramine maleate)

New FDA Approved
Formulations

 for the relief of cough and symptoms associated with upper respiratory allergies or a common cold in adults 18 years of age and older
Tuzistra XR is administered as an oral dose of 10mL every 12 hours and may be taken with or without food.

New FDA Approved
Formulations


05.27.2015
Actavis Receives FDA Approval for
VIBERZI (eluxadoline) for the
Treatment of Irritable Bowel
Syndrome with Diarrhea (IBS-D) in
Adults

New FDA Approved
Formulations



 as a twice-daily, oral treatment for adults suffering from irritable bowel syndrome with diarrhea (IBS-D). VIBERZI
(eluxadoline) has mixed opioid receptor activity, it is mu receptor agonist, delta receptor antagonist a kappa receptor agonist.

Abused Meds

Tussionex


10 ml/day is normal dose
“Small” quantities may actually be large

Abused Meds





Promethazine with codeine
Party substance
Prefer the purple
Contraindicated under 6 years old
More than 8 ounces

Abused Meds


Hydrocodone pain meds
Lortab vs Lorcet vs Vicodin vs Norco

Abused Meds


Hydrocodone pain meds
Lortab vs Lorcet vs Vicodin vs Norco

Lortab and Lorcet no longer exist


Norco 5, 7.5, 10 – 325 mg APAP
Vicodin 5, 7.5, 10 – 300 mg APAP

Non-controlled substances can still be abused







Alcohol
Gabapentin
Clonidine
Dextromethorphan
Promethazine
Diphenhydramine
Krill oil?





Herbs

Salvia divinorum

Jimsonweed
Epoetin alfa
Nitrous oxide
Volatile solvents
Aryl nitrites

 http://www.usatoday.com/story/news/n ation/2015/04/07/mississippi-spiceoverdoses/25428467/

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