Transcript 4b-D-D-Int,New Drug Development Rx Writing

Reading assignments:
Katzung’s Basic & Clinical Pharmacology,
13th Edi,Ch-1,p10-19, Ch-2,p37-38
Ch-4,p69-71,Ch-66,p1119-1131,
Ch-65,p1109-1117 ;
Sanjib Das
M.B.B.S.,M.D.,P.G.D.H.A.
1
Learning Objectives
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Determine the different factors modifying drug action
Explain in detail about different processes involved in drug
development
Discuss pre-clinical (animal) studies and different phases of clinical
trials
Explain the concepts of investigational New drugs (IND) and New
drug application (NDA)
Describe different components of prescription writing
Describe different components of prescription writing
Demonstrate how to write a good prescription
Explain the concepts of rational Prescribing
Describe the selection of Personal (P-) Drugs
Discuss the concepts of Essential Medicine
Define terms associated with drug use behavior (Compliance,
adherence and concordance)
Recognize legal terms such as Comprehensive Drug Abuse
Prevention and Control Act
Identify different schedules of drugs
Identify the US FDA teratogenic risk categories
2
Case Based Learning
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Julie Smith is a 35 year old female nurse working with
isolation wards of a community hospital.She has been taking
oral contraceptive pills since last couple of years .Recently
couple of months ago she took some medication as
prophylaxis after having an exposure to a meningococcal
meningitis patient. On the next month she came to
Gynaecology OPD with complaint of amenorrhea .
Laboratory test shows a positive pregnancy test although
she was still on contraception..
1.Figure out the possible underlying cause of her
contraception failure .
2.Discuss in details about various types of D-D Interactions
that can take place both in Pharmacokinetic (absorption,
plasma protein binding level, metabolism & elimination ) &
pharmacodynamic (receptor level interactions) level with
some examples
3
NBME
Drug Interactions
Pharmacokinetic mechanisms:
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Absorption: rate and extent of drug absorption may be
altered; reduction in rate of absorption is not often clinically
important; reduction in extent of absorption may result in
subtherapeutic serum levels. Examples:

Cholestyramine: resin binds with drugs and prevents
absorption

Antacids: metals chelate tetracyclines and fluoroquinolones
preventing their absorption
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Anticholinergics (e.g., atropine): decrease gastrointestinal
motility and slow absorption of many drugs
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Gastrointestinal motility alteration: may alter absorption; for
example, delay absorption of some weak organic acids
Drug Interactions
NBME
Pharmacokinetic mechanisms:
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Distribution:
○
Displacement of drugs from plasma protein binding sites
Plasma Protein Binding:
Oral hypoglycemic agents (e.g., tolbutamide);
Oral anticoagulants (e.g., warfarin);
Antimetabolites (e.g., methotrexate)
○
○
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Displacement of drugs from tissue binding sites (eg. digoxin
displacement by quinidine)
pH gradients: example, weak organic bases accumulate in milk
which is acidic in comparison to blood
Biotransformation: see inducers and inhibitors presented on
earlier slides
Drug Interactions
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Pharmacokinetic mechanisms:
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Excretion:
○
Alkalinization of urine (sodium bicarbonate)
enhances excretion of weak organic acids
○
Acidification (ammonium chloride) of urine
enhances the excretion of weak organic bases
○
Block tubular secretion (probenicid inhibition of
penicillin secretion)
NBME
Drug Interactions
NBME
Pharmacodynamic mechanisms:
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Additive or synergistic effect is often observed when drugs with
similar pharmacologic effects (e.g., Valium and ethanol) are
administered concurrently
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Conversely, drugs with opposing pharmacological effects
(propranolol and isoproterenol; naloxone and morphine) may
reduce response to one or both drugs
Combined toxicity: combined use of two or more drugs,
each with toxic effects on a given organ
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Can enhance likelihood of organ damage
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Administration of two nephrotoxic drugs (aminoglycoside and
vancomycin) can produce kidney damage even when dose of
either agent alone may have been insufficient to produce toxicity
Which of the following agents if taken
concomitantly might reduce effectiveness
of Tetracycline/FQs?
(A)A calcium containing health tonic
(B)An antihistamine
(C)A nonsteroidal anti-inflammatory
(D)An anxiolytic
(E)A peg of whisky
A jaundiced one-day-old premature infant with an elevated
free bilirubin is seen in the premature-baby nursery. The
mother received an antibiotic combination preparation
containing sulfonamide for a urinary tract infection (UTI) one
week before delivery. You suspect that the infant's findings
are caused by the sulfonamide because of the following
mechanism:
(A)Enhanced synthesis of bilirubin
(B)Competition between the sulfonamide and bilirubin for
binding sites on albumin
(C)Inhibition of bilirubin degradation
(D)Inhibition of urinary excretion of bilirubin
(E)None of the above
A 35 years old female has ingested toxic amount of a
drug which she was receiving in the treatment of her
Headache. Routine Urine examination revealed significant
lowering of urinary PH. Doctor prescribed Sodium
Bicarbonate by parenteral route with a Pharmacotherapeutic
concept that
a. Sodium Bicarbonate being alkaline would neutralize
acidic urine by its chemical action
b. Sodium Bicarbonate would take care of metabolic
acidosis
c. Sodium Bicarbonate would hasten the excretion of
ionized aspirin by creating an alkaline environment in the
tubular fluid
d. Sodium Bicarbonate is known for chelation of basic
drugs
e. Sodium carbonate reduces the threat for Acute Tubular
Necrosis which might occur during acideurea.
Which of the following best describes the use of
celecoxib in the treatment of rheumatoid arthritis in a
55-year-old man with severe cardiovascular disease?
A.
B.
C.
D.
E.
Contraindicatory therapy
Answer: A
Lethal therapy
Idiosyncratic therapy Cox-2 inhibitors are
Life saving therapy contraindicated in patients
with a history of cardiovascular
disease; lack of production of
Preferred therapy
PGI2 to offset the actions of TXA2
Drug evaluation definitions
Single-blind
study
A clinical trial in which the investigators-but not the
subjects-know which subjects are receiving active drug
and which are receiving placebos
Double-blind
study
A clinical trial in which neither the subjects nor the
investigators know which subjects are receiving placebos;
the code is held by a third party
IND
Investigational New Drug Exemption; application for FDA
approval to carry out new drug trials in humans; requires
animal data
NDA
New Drug Application; FDA approval to market a new drug
for ordinary medical clinical use
Placebo
An inactive "dummy" medication made up to resemble the
active investigational formulation as much as possible
Learning objectives
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Understand the process of drug
development and evaluation
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Understand the clinical trial
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Be familiar with regulation processes
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Be familiar with informational systems
available to practitioners.
Drug evaluation definitions
Phases I, II,
and III of
clinical trials
Three parts of a clinical trial that are usually carried out
before submitting an NDA to the FDA
Positive
control
A known standard therapy, to be used along with placebo,
to fully evaluate the safety and efficacy of a new drug in
relation to the others available
Mutagenic
An effect on the inheritable characteristics of a cell or
organism-a mutation in the DNA
Teratogenic
An effect on the development of an organism resulting in
abnormal structure or function; not generally heritable
Carcinogenic
An effect of inducing malignant characteristics
Drugs developed for diseases in which the expected
number of patients is small. Some countries bestow certain
Orphan drugs
commercial advantages on companies that develop drugs
for uncommon diseases
FEDERAL REGULATIONS
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Safety and efficacy of drugs are regulated by the Food and Drug
Administration (FDA)
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Animal Testing (see text for details)
 Acute toxicity: All drugs; single dose of the agent up to a lethal dose in 2
species (rodent; non-rodent)
 Subacute and chronic toxicity: Most drugs tested according to the least
amount of time proposed for humans; i.e., 2-4 weeks (subacute) or 6-24
months (chronic), in at least 2 species
 Pharmacological profile
 Reproductive toxicity
 Carcinogenesis
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Notice of Claimed Investigational Exemption for a New Drug (IND) is
filed with (FDA) once a potential drug is judged ready to administer to
humans.
The development and testing process required to
bring a new drug to market in the USA.
NBME
Human Testing
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NBME
Clinical trials are divided into four phases (see text for details):
 Phase 1: first time the agent has been administered to humans
○ First dose is always a placebo
○ Patient's anxiety may produce psychic or physiologic changes, placebo will keep
investigator from confusing these artifacts with drug actions
○ Goal is to find maximum tolerated dose
○ Testing is never double-blind and usually involves 20-30 patients
○ No clear cut-off between Phase 1 and Phase 2
 Phase 2: first attempt to determine clinical effectiveness of test agent; tests
may be single-blind or double-blind and involve hundreds of patients
 Phase 3: extensive testing of a drug's efficacy and toxicity
○ Undertaken only if data from Phase 2 are positive
○ Phases 1 and 2 studies are usually conducted by clinical scientists, but phase 3 may
include physicians in private practice
○ After completion, company files New Drug Application (NDA) with FDA
○ Fewer than 10,000 subjects are usually tested before Phase 4.
 Phase 4 (post-marketing surveillance): adverse effects and toxicity become
most evident (incidence of aplastic anemia in chloramphenicol therapy is
1/40,000)
•In which phase patients of the testing drug is typically included in the study
(A)Lab testing
(B)Animal testing
(C)Phase I
(D)Phase II
(E)Phase III
Informed Consent
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Required for Phase 1, 2, and 3 subjects
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Must be in writing for Phase 1 and 2
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Peer review (Committee on Human
Experimentation) protects the interest of
subjects, investigators, & institutions
Orphan Drugs
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In the USA, current legislation provides for tax
relief and other incentives designed to
encourage the development of orphan drugs.
Objectives
Define a prescription and the classification
of medications
 Compare and contrast the various
schedules of controlled substances
 Compare and contrast a prescription
medicine and a non-prescription medicine
 List the component elements of the
prescription
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Objectives cont’d
List the component elements of a
controlled substance prescription
 Classify controlled drugs by their schedule
 Describe writing conventions associated
with prescription writing
 Provide examples of “look alike,” “sound
alike” prescription medicines, including
trade names
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Objectives cont’d
Provide examples of confusing
abbreviations used in prescription writing
 Describe important prescription writing
precautions for traditional and controlled
substance prescriptions
 Define the “off label” use of a drug
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Prescription Order Writing
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Definition: A prescription is a written,
verbal, or electronic order from a prescriber
(e.g., physician, dentist, podiatrist, nurse
practitioner) to a pharmacist for a particular
medication for a specific medication at a
certain time.
Classification of Medications
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Prescription= “legend” drug or medication
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Prescription product label reads:
“Caution: Federal Law Prohibits
Dispensing without a Prescription.”
Types of Prescriptions
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Generic The nonproprietary name provided
by the United States Adopted Name (USAN)
Council
 syn. Chemical Name
 e.g., amoxicillin, fluoxetine, diazepam, aspirin

Brand Name The proprietary name or
registered trademark name provided by the
pioneer (innovator) pharmaceutical company
who holds the patent on the drug
 e.g., Prozac®, Viagra®, Xanax®
Types of Prescriptions cont’d

Compounded Requires the preparation of one
or more active ingredients with one or more
pharmaceutical necessities, e.g., suspending
agent, flavoring agent, to create a finished
product.
For example, an oral compounded prescriptions may be used to
facilitate the administration of a solid dosage form that is not
available in liquid form for patients unable to swallow a solid dosage
form.
○ e.g., pediatric, geriatric
Types of Prescriptions cont’d
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Control Substance Distribution of certain medicines
with abuse potential is controlled through the
Comprehensive Drug Abuse Prevention and Control Act
of 1970
This Act is regulated and enforced by the federal Drug
Enforcement Agency (DEA)
 MDs must be registered with the DEA to prescribe
those drugs under the control of this act.
 Re-registration is mandatory every three years.
*A partial listing of controlled substances is demonstrated
in Appendix A. Further examples of drugs by schedule
are found at http://www.dea.gov/pubs/scheduling.html
Types of Prescriptions cont’d
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New An original prescription order
dispensed for the first time.
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Refill A repeat dispensing of the original
prescription order.
 Usually, encompasses patients on maintenance therapy,
e.g., digoxin, phenytoin, lovastatin, potassium chloride.
Schedules of Controlled Substances
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Schedule I  No medical use with a high
abuse and dependence potential
 A physician cannot write for this schedule of drugs
 e.g., LSD, Marijuana*, Heroin, Mescaline (Peyote), 1-(1-
Phenylcyclohexyl)pyrrolidine (i.e., PCP).
*Twelve states have laws regulating the medical use of
marijuana- AL, AZ, CA, CO, HI, ME, MD, MT, NV, OR, VT,
WA
Schedules of Controlled Substances
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Schedule II  A written prescription is required for this
schedule. However, there are no refills allowable.
 Only in an emergency situation is an oral order allowable and
acceptable to the dispenser.
 Must be followed by a written prescription within 72 hours.
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In some states (formerly IL), the physician must complete a triplicate
prescription form to prescribe Class II in ink.
The physician should write out the actual amount prescribed besides giving
an Arabic Number or Roman Numeral for the quantity.
 This discourages forging or “alteration” of the prescription.
In Illinois, a written prescription for this schedule must be dispensed within
90 days, i.e., 3 months, of issuance or it expires.
 e.g., amphetamines, meperdine HCl, cocaine, secobarbital sodium
Multiple Prescriptions for Schedule II Controlled Substances
DEA Rule
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12/19/07 – Approved federal legislation to allow
prescriber to write >1 prescription (not more than a
90 day supply total) for CII controlled substances
in certain circumstances.
▪ Legitimate medical purpose.
▪
Instruction on each prescription indicating earliest date
to dispense the prescription.
▪
This situation does not create an undue risk of diversion
or abuse.
▪
Applicable state laws permit this practice including
Illinois.
▪
Prescriber is in compliance with all other state and
federal
laws.
Schedules of Controlled Substances
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Schedule III Drugs in this schedule have
a moderate abuse and dependence
potential
 May be prescribed in writing or through a verbal order.
 May be refilled up to five times within a six month interval
from the date of issuance.
 e.g., glutethimide, chlorphentermine, phenmetrazine,
anabolic steroids
Schedules of Controlled Substances
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Schedule IV Drugs in this schedule are
considered to have low abuse and low
dependency potential
 May be prescribed through writing and through a verbal
order.
 May be refilled upto five times within a six month interval
from the date of issuance.
 E.g., alprazolam (Xanax®), pentazocine (Talwin®),
flurazepam (Dalmane®)
Schedules of Controlled Substances
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Schedule V Drugs in this schedule have the
least amount of abuse potential and an unlikely
dependency
 Consists primarily of medications that contain limited quantities
of certain narcotic and stimulant drugs generally used as antitussives, antidiarrheals, and analgesics
 Can be purchased OTC by the patient who signs a registry
 e.g., Robitussin AC, Parepectolin, Kaopectolin PG
Nonprescription Medications
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Can be purchased at pharmacies and retail outlets
without a prescription (syn. Over-the-counter [OTC]
products)
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To date, 99 drugs and/or drug dosage forms have been
“switched” from prescription to OTC status (Note
Appendix AA)
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Besides South Africa, the US is the only country NOT to
have a “third class” of drugs. That is, available through
the pharmacist.
 FL has a “pharmacist only” class of medications
 BTC being considered by FDA
National Coordinating Council for Medication Error
Reporting and Prevention (NCC-MERP) -- Founding
Members

American Association of Retired Persons;
American Health Care Association;
American Hospital Association;
AMA; American Nurses Association;
American Pharmacists Association;
American Society of Health-System
Pharmacists; FDA; GPIA; JCAHO; National
Association of Boards of Pharmacy;
National Council of State Boards of
Nursing, Inc; PhRMA; United States
Pharmacopeia
NCC-MERP Recommendations to
Improve Error-Prone Aspects of
Prescription Writing
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All prescriptions must be legible.
Prescribers should move to a direct,
computerized, order entry system.
Handwriting examples:
Can you read this?
Component Elements of the
Prescription
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Heading Physician’s name, practice
address and telephone number, DEA
number
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Date prescription is written
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Patient Information Name, address, age
(esp., if for a pediatric or geriatric patient)
Component Elements of the
Prescription
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Body of the Prescription (Note: Exhibit)
 RX Take Thou. Name of the prescribed drug or
drug product. Also included is the strength of the
medication, the number or quantity of the prescribed
drug in addition to the dosage form
○ DO NOT use abbreviations for drugs prescribed unless the
abbreviation is official, e.g., SSKI (Saturated Solution of
Potassium Iodide), NSS (Normal Saline Solution), HCTZ
(Hydrochlorothiazide), NTG (Nitroglycerin), MTX
(Methotrexate)
○ Avoid “unofficial” abbreviations
Component Elements of the Prescription - Body
of the Prescription (cont’d)
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Sig Signatura (i.e., Mark Thou).
Directions for use, e.g., one cap every 8
hrs.
 Avoid “ut dictum” or “as directed.” Units should
be spelled out rather than writing “U.”
 Latin abbreviations (Appendix B) are acceptable
as well as plain English
 Commonly confused Latin abbreviations
include: qd, qod
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Refills “N” times or NR. Leaving this
section blank implies that the prescription
is non- refillable.
Dangerous Abbreviations
Abbreviation
U
 µg
 Q.D.
 Q.O.D.
 MS, MSO4,
MgSO4
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Intended Meaning
Units
Micrograms
Every day
Every other day
Morphine sulfate or
magnesium sulfate?
More Dangerous
Abbreviations
SC or SQ
 TIW
 D/C
discontinue
 HS
bedtime?
 cc
 AU, AS, AD
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
I.U.

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Subcutaneous
Three times a week
Discharge;
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

Half strength;
Cubic centimeters
Both ears, left
ear, right ear
International units
Component Elements of the Prescription - Body
of the Prescription (cont’d)
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Generic Authorization Physician signature on the
“dispense as written” or “may substitute” line
“No Child Resistant Packaging” Authorization All
legend drugs intended for oral use must be dispensed
by the pharmacist to the patient in containers having
safety closures unless the prescribing physician or the
patient specifically requests otherwise.
 A request for a non-child resistant container may be applied to a
single prescription or to all of the patient’s dispensed
medications.
 The pharmacist should clarify the patient’s desires, obtain and
file a signed waiver request, and maintain the information in the
prescription computer for future reference.
 Exception: Nitroglycerin (NTG) containing products.
Component Elements of the Prescription - Body
of the Prescription (cont’d)

Signature Legible in indelible pencil or
pen. Signature selections:
 May substitute_______________________
 Dispense as written___________________
•
DEA Number If necessary and, usually,
within the heading of the prescription blank
along with the physician’s practice
information
Writing Conventions

For compounded prescriptions, when units
are not given, solids are assumed to be in
grams (g) and liquids in milliliters (ml).
 Never write a decimal without a zero preceding it, e.g., 0.15 g
Clindamycin HCl. This helps to minimize an error in translation
 Never write a decimal with a zero following it, e.g., Propylene
Glycol 6.0, Propylene Glycol 6
 e.g., Rx
Clindamycin HCl
0.15
Propylene Glycol
6
Lavacol qsad
30
Sig:
Apply to affected area twice daily
Writing Conventions (cont’d)
 Sometimes a vertical line is used for the decimal
point, although, conceivably, it could be
confused as a number one.
____
○ e.g., Rx
Chlorpheniramine
Aspirin
Dispense Caps #12
Sig:
0 l 002
0 l 325
One capsule po four times daily
for allergy and pain
Writing Conventions (cont’d)

Liquid household measures
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






Milliliter = ml
1 teaspoonful = 5 ml
1 tablespoonful = 15 ml
2 tablespoonfuls = 30 ml (approximately one ounce)
8 fluid ounces ~ 240 ml
One pint = 16 fluid ounces = 473 ml
One quart = 32 fluid ounces = 946 ml
One gallon = 4 quarts = 8 pints = 3750 ml
gtts = drops (e.g., oral, ophthalmic, ear, topical)
Writing Conventions (cont’d)

Solid weights





mcg
mg
g
gr
=
=
=
=
microgram
milligram
gram
grain (old apothecary system reserved
for “older,” traditional medications).
Note for these one grain is equal to 60 mg.
Otherwise, one grain = 64.8 mg.
○ e.g., nitroglycerin, 1/150 gr, 1/200 gr, 1/400 gr;
phenobarbital, ¼ gr., ½ gr.,1 gr.;
thyroid ¼ gr, ½ gr, 1 gr.
Writing Conventions (cont’d)

Be very cautious about drug names that
“sound/look” alike (Appendix C).
http://www.nacds.org/wmspage.cfm?parm1=1915

Avoid using “unofficial” abbreviations for
drugs/drug product names, e.g., PCN (Penicillin),
SMX-TMP (Sulfamethoxazole-Trimethoprim), TCN
(Tetracycline), KCl (Potassium Chloride), MOM (Milk
of Magnesia). If confused, contact the pharmacist.
Prescription Writing Suggestions

Intended to ensure patient safety and
minimize pharmacist intervention on behalf
of the prescriber and the patient.

Keep all prescription blanks in a safe place
out of patient reach. This avoids the
temptation and disappearance of blanks.
Further, this procedure minimizes the
number of prescription pads in use.

Use a separate prescription blank for
each prescribed medication.
Prescription Writing Suggestions

Ensure that refill directions are included
on every prescription. Is it refillable or
not?
If refillable, indicate the number of times or
the duration of time that refills are
authorized. It will save the prescriber time
and interruptions in the long run. Legally,
aside from refill limitations associated with
controlled substances, a prescription refill
for a conventional, non-controlled
medication has a one year expiration time.
Prescription Writing Suggestions

Attempt to make the prescription order
alteration proof.

Use indelible pencil or ink and for controlled
substances write the number and spell it out.
Otherwise, for example, a “XII” can be forged to
read “XXX.” Use the same pen or indelible
pencil for the entire prescription. If a mistake
is made, e.g., number of tablets, cross out the
mistake, write/print “error” above it, and then
initial it.
Prescription Writing Suggestions

Avoid writing a prescription for a large quantity of
drug unless it is absolutely determined that such a
quantity is necessary.
For an anticipated chronic medication, it is better to start
with a lower number at first in the event that the patient
cannot tolerate it because of side effects. Think also of
the economic considerations. Insurance plans will limit
the amount to one to three months at most.

When an institutional prescription blank is used, the
prescriber should clearly print his/her name,
address, DEA registration number on the blank.
Prescription Writing Suggestions for
Controlled Substances

Again, this is intended to ensure patient safety
and minimize pharmacist intervention on
behalf of the prescriber and the patient.

Use a separate prescription blank for each
substance prescribed.

Maintain only a minimum stock of controlled
substances in the medical bag, and it should be
taken by the physician while away from the
automobile. Keeping the medical bag locked in the
automobile trunk is not always an effective
deterrent.
Prescription Writing Suggestions for
Controlled Substances
During the drug history, if a patient concedes that
he/she has received a controlled substance
prescription from another physician, consult that
physician or the hospital records, and/or examine
the patient to decide if a controlled substance
should be prescribed.
 Do not allow the patient to dictate the controlled
substance, if any, to be prescribed. The patient
may be “doctor shopping.”
 Maintain an accurate record of controlled
substance products dispensed as required by the
Controlled Substances Act.

Prescription Writing Suggestions for
Controlled Substances

A prescription order blank should only be used for
writing the prescription.

Do not use it to write a note and/or information for
the patient. An unscrupulous drug dealer or
abuser could erase the information easily and use
the blank to forge a prescription drug.
Prescription Writing Suggestions for
Controlled Substances

The prescriber should use the pharmacist as a
valuable resource when needed. Also, assist the
pharmacist when he/she inquires to verify
information about a prescription order. A
corresponding responsibility/liability rests with the
pharmacist who dispenses the prescription order.

Telephone the nearest DEA field office to secure
and/or furnish information. The call is held in
strictest confidence.
Unlabeled (syn Off-Label) Use
(Indication)

Serendipitous observations (e.g., decreased migraine
headache attacks while maintained on β-blockers for
cardiovascular therapy; sildenafil citrate clinically
evaluated for lowering blood pressure demonstrating
use for erectile dysfunction) and therapeutic
interventions of physicians have led to medicines being
prescribed for unlabeled use for which the drug has not
been approved by the FDA.

The off-label use is supposed to be based upon a
rational scientific theory, expert medical opinion, or
evidence based on sound clinical trial(s).
Unlabeled (syn Off-Label) Use
Commonly used for depression, cancer, HIV/AIDS, dermatological
disorders, and migraine
.
Common in the pediatric population—danger ↑ AEs.
In 2001, ~73% off label prescriptions were not supported by
scientific evidence.
Unlabeled (syn Off-Label) Use
(Indication)

The FDA makes clear that it neither has, nor desires, the
authority to compel physicians to adhere to only “official”
labeled indications. Simply, experience has
demonstrated that the official indications “lag” behind
scientific knowledge and the scientific/medical literature.
Unlabeled (syn Off-Label) Use
(Indication)

A Supplemental New Drug Application (NDA) may be
filed by the drug manufacturer when approval is sought
for an additional indication for a drug already approved
for another indication. It has been estimated that 40%
of all prescriptions are written for indications for which a
Supplemental NDA has not been filed. While this
process is less demanding, drug manufacturers do not
want to invest the time, energy, and $$ to do so.

Consequently, this has resulted in 75 to 90% off-label
prescribing for infants and children. The caveat is less
than desirable dosing and warnings for the pediatric
patient with increased incidence of adverse effects.
Single Patient Compassionate Use

A FDA-requested mechanism for a physician to
use a drug in a single patient, usually in a
desperate situation when there is no response
to other therapies or in which there is no
approved or recognized treatment available.
Single Patient Compassionate Use

Approval for a compassionate use may be sought in the
following situations when a(n):
 IND is in effect, but the drug is still in the early stages of testing.
 IND is in effect, but the intent of the drug use is not for the
purpose described in the IND.
 drug has an IND, but it is not marketed.
 drug has had previous FDA approval but has been withdrawn
from the market because of questions regarding its safety.
 drug is being investigated or marketed outside of the US, but no
IND is in effect within the US.

Often, the FDA will permit the proposed use under a
commercial sponsor’s IND or under a new IND filed by
the physician in behalf of an identified patient.
References
 Scott SA. “The Prescription,” in Remington: The
Science and Practice of Pharmacy, 21st Edition,
A. Gennaro, Chairman, Editorial Board and
Editor, Lippincott Williams and Wilkins, Baltimore
MD, 2005, pp. 1823-1839.
 http://www.dea.gov/pubs/scheduling.html
 http://www.nacds.org/wmspage.cfm?par
m1=1915

Updated: March 24, 2010