Transcript Some considerations for IV additives

IV Workshop: Regulation Updates
and New Protocols
200 Nohea Kai Drive, Lahaina, HI 96761, USA
Paul S. Anderson, NMD
Hawaii DocTalks
Thursday 3/2/17 9:00 - 11:30am
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Dr. Paul Anderson – Financial Disclosures:
Ownership interest in:
• Advanced Medical Therapies Clinic Seattle, WA
• Advanced Applications in Medical Practice Seminars
• ConsultDrAnderson.com
Educational consultant for:
• Imprimis Pharmaceuticals
• Canadian College of Naturopathic Medicine
• Bastyr University
• University of Bridgeport
• Vermont Association of Naturopathic Physicians
• Key2Health
• Emerson Ecologics
• Power to Practice
• IV Nutritional Therapy Group
• Sanoviv Hospital
NOTE: Dr. Anderson is paid a fee to consult with the above and derives no financial gain from the sale of
any product, referral or service. He is paid as an educational / medical consultant.
Dr. Anderson - Disclosures
Ownership interest in:
• Advanced Medical Therapies Clinic Seattle, WA
• Advanced Applications in Medical Practice
• ConsultDrAnderson.com
Educational consultant:
• Imprimis Pharmaceuticals
• Canadian College of Naturopathic Medicine
• Bastyr University
• University of Bridgeport
• Vermont Association of Naturopathic Physicians
• Key2Health
• Emerson Ecologics
• Power to Practice
• IV Nutritional Therapy Group
• Sanoviv Hospital
NOTE: Dr. Anderson is paid a fee to consult with the above and derives no financial gain from the sale of any
product, referral or service. He is paid as an educational / medical consultant.
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Outline
• Part – 1
•
•
•
•
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USP-FDA Rule changes
What you can and cannot do without a clean space / hood
How to comply
FDA Update
More resources
• Part – 2
•
•
•
•
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Critical Clinical Thinking in IV Therapy
Formula Customization Basics
Dose Ranges and Frequency
Sequencing of IV’s for Maximum Synergy and Efficacy
Free Resources
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AND:
We can do as much ‘Q&A’ as possible – that way
we all learn more!
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Who are the players and what roles do they
play?
•
•
•
•
A. USP
United States Pharmacopeia, a legally recognized compendium of standards for drugs, published by the
United States Pharmacopeial Convention, Inc., and revised periodically; it also includes assays and tests for
determination of strength, quality, and purity.
B. FDA
An agency of the United States Department of Health and Human Services whose principal purpose is to
enforce the Federal Food, Drug and Cosmetic Act. The agency insures that foods for sale in the United States
are safe, pure, and wholesome; that drugs and therapeutic devices are safe and effective; that cosmetics are
harmless; and that all these products are correctly labeled and packaged. The FDA is also responsible for
enforcing the federal act that requires informative labels on any household product that is toxic, corrosive,
irritant, or inflammable or generates pressure through decomposition or heat.
If a product in interstate commerce is proved to be faulty, the FDA is authorized to bring court action or seize
the adulterated or incorrectly labeled merchandise and to prosecute the responsible person or company.
C. State Health Department – Professional Board
Any State Department of Health or Regulatory Board / Agency has the authority to provide additional
“interpretation” and additional rulemaking to the implementation of FDA, USP or other Federal laws or
guidelines. The Health Department may do this for all health care professions in many States and each
Board may do this for its profession or professions.
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Non-sterile products (oral, topical etc.)
USP Chapter <795>
USP Chapter <795>: Pharmaceutical Compounding—Nonsterile Preparations: This General Chapter provides
guidance on applying good compounding practices in the preparation of nonsterile compounded formulations
for dispensing and/or administration to humans or animals. The latest revision which became official May 1,
2011 includes categories of compounding (simple, moderate, and complex); definitions for terms (e.g., beyonduse date, hazardous drug, stability); and criteria for compounding each drug preparation (e.g., suitable
compounding environment, use of appropriate equipment).
ii. Implications
• Chapter 795 preparations include all non-sterile medications for all practical purposes. These are dermal,
oral, sublingual and like compounds.
• Chapter 795 preparation that is compounded generally follow the “patient specific” rule and in most States
cannot be used other than in the setting of prescription for one patient. It can be used in office for the
patient prescribed for but not for any other patient.
• What is NOT included? Any preparation that is “manufactured” (or non-compounded) can be sold and used
for in office purposes or dispensed to patients. Manufactured product does not fit the “patient specific”
rule.
* If your State is not enforcing the patient specific rule you may be able to obtain and use compounded product for office use. Please
check with your State Board of Pharmacy.
** NOTE: What is the “Patient Specific” rule? The FDA now requires all compounded preparations to be patient specific (not the USP). The FDA has determined that
they will not consider a compounder a manufacturer if the compounder processes all orders as patient specific. (See below).
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Sterile Product (IM, IV, Nebulized, Eye drops etc.)
USP Chapter <797>
Chapter 797: Pharmaceutical Compounding—Sterile Preparations—This General Chapter provides procedures and
requirements for compounding sterile preparations. General Chapter <797> describes conditions and practices to prevent
harm to patients that could result from microbial contamination, excessive bacterial endotoxins, variability in intended
strength, unintended chemical and physical contaminants, and ingredients of inappropriate quality in compounded sterile
preparations.
ii. Implications
• Chapter 797 preparations include all sterile medications. These are inhaled, ophthalmic, injectable and like compounds.
• Chapter 797 preparations that are compounded generally follow the “patient specific” rule and in most States cannot be
used other than in the setting of prescription for one patient. It can be used in office for that patient but not for any other
patient.
• What is NOT included? Any preparation that is “manufactured” (or non-compounded) can be sold and used for in office
purposes or dispensed to patients. These products we often see as “stock” product and examples include stock IV bags,
stock medications, stock injectable medications and the like. No compounded (503A) product falls into this category. [See
the note about 503B medications at the end of this paper].It does not generally fit the “patient specific” rule.
* If your State is not enforcing the patient specific rule you may be able to obtain and use compounded product for office use. Please
check with your State Board of Pharmacy.
** NOTE: What is the “Patient Specific” rule? The FDA now requires all compounded preparations to be patient specific not the USP.
The FDA has determined that they will not consider a compounder a manufacturer if the compounder processes all orders as patient
specific. (See below).
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CDC involvement: Site preparation rules for IM versus
IV versus IA injections & IV access device rules
1. IM, Subcutaneous, ID or an IV In place less than 30-45 minutes:
1A. Access: Any appropriate device (Butterfly, Catheter…)
1B. Site Preparation: Any reasonable preparation of the skin (isopropyl alcohol is acceptable)
2. IV In place More than 30-45 minutes:
2A. Access: Catheter (IV cannula) or central access only
2B. Site Preparation: more than 0.5% chlorhexidine preparation with alcohol - (Hibiclens etc…) or like prep
only. If there is a contraindication to chlorhexidine, tincture of iodine, an iodophor, or 70% alcohol can be used
as alternatives
3. Central Venous Access Device (CVAD):
Skin preparation entails preparing clean skin with a more than 0.5% chlorhexidine preparation with alcohol
before CVAD access. If there is a contraindication to chlorhexidine, tincture of iodine, an iodophor, or 70%
alcohol can be used as alternatives.
4. Intraarticular injections or aspirations:
Using sterile procedure prepare skin with a more than 0.5% chlorhexidine preparation with alcohol before
CVAD access. If there is a contraindication to chlorhexidine, tincture of iodine, an iodophor, or 70% alcohol can
be used as alternatives.
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Frequently Asked Questions:
Can I use anything for “office use” anymore?
• Any non-compounded medication (currently) can be used, and in
some States the patient specific rule is not currently enforced by the
Board of Pharmacy or Department of health.
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Frequently Asked Questions:
What is the “patient specific” rule and does it apply to all prescription
products now?
• It essentially states that a pharmacy can still offer a compounded
prescription on physician order if it is specific to a patient and then
the compounding pharmacy will not be considered a manufacturer
for regulatory purposes. It renders that prescription specific to the
patient it was compounded for.
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Patient Specific Prescriptions
• Some (most) States currently require patient specific
prescriptions for all compounded medications. Some do not,
but likely will soon. The following is a statement
amalgamated from three pharmacy experts who all agreed
to give input to the genesis of this rule (and the variations of
it we see):
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Patient Specific Prescriptions
• “The FDA decided that if compounding pharmacies process
all orders as “patient specific” prescriptions the FDA will
choose not to evaluate compounding pharmacies as
manufacturers. Office Use is still on the books in California
and some other states, but even the Board of Pharmacy
supports the patient specific requirement.”
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Patient Specific Prescriptions
• Any exceptions:
1. If the product is ordered from a 503 (b) manufacturing facility –
of which there are just a few in existence.
2. A bill to allow “office use” MAY be forwarded to the US
Congress and if it passes would relax this rule.
* But that is NOT the case now.
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Frequently Asked Questions:
What are the rules for single and multi-dose sterile vials?
• These have not changed:
• 28 day use for multi-dose (unless manufacturer specifics otherwise)
• Stored in refrigeration between use (unless manufacturer specifics otherwise)
• Single use for single-dose product – with some qualifications.
• Outside an ISO-5 environment = Up to two entries & one use
• Inside an ISO-5 environment = Six hours use – if not removed
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Engineering controls to minimize vial punctures
& contamination (both with 0.2 micron air filter):
Single-dose use
(capped luer)
Multi-dose
use (spring
luer adaptor)
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Frequently Asked Questions:
What rules apply to me as a clinician and to my clinic as a facility?
• Many apply. The presentation and attached document (the ‘pdf’) will
spell out as succinctly as possible the intersecting rules relating to
clinical practice that are involved in compounded and manufactured
prescription use, injections and other forms of medications and
guidelines influenced by multiple Federal agencies.
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An excellent question is “I am not a pharmacist or pharmacy, how can an
FDA Pharmacy “Act” be applied to me as a Physician?” - USP Section 503A
The IACP (see reference at the end of this quote) have reviewed the Act and rules
and state: “503A applies to “Traditional Compounders” and extends to
Pharmacist as well as Physician:
“If a "traditional compounder", defined as a licensed pharmacist or licensed
physician, meets ALL conditions within Section 503A, the compounder is exempt
from THREE sections within the Food, Drug, and Cosmetic Act;
(1) Section 501(a)(2) (concerning current good manufacturing practices); (2)
Section 502(f)(1) (concerning labeling or drugs with adequate directions for
use); and (3) Section 505 (concerning the approval of drugs under new drug
applications or abbreviated new drug applications).”
International Academy of Compounding Pharmacists. 2014. - IACP Comparison of
503A and 503B
The Drug Quality and Security Act of 2013 http://c.ymcdn.com/sites/www.iacprx.org/
resource/resmgr/imported/IACP%20Comparison%20DQSA%20503A%20and%20503B%2001202014.pdf
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Frequently Asked Questions:
I went to a presentation a few years ago and they said my IV bags fit
the “immediate use exemption” and therefore I did not need a hood?
• Most of the immediate use exemption is no longer valid.
* A few items meet this, but not very many. In the following
presentation and the main document a great deal of detail is given to
this rule.
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Frequently Asked Questions:
I have heard I need a clean room to make my syringes and IV bags. Is
that true?
• Possibly. The rules depend upon the “risk level” of what you are
making. Simple compounds may not require this and many
commonly compounded injections and IV’s will. This is a bit complex
but a great deal of information in regard to this is contained in the
following presentation and the main document.
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Frequently Asked Questions:
I have a “fume hood” already, can I use that?
• If it is really a fume hood then no. Those hoods are used to prepare
or manipulate dangerous products and exhaust the workspace air out
of the building. The laminar flow hoods for compounding move
purified air through the workspace and out of the hood, increasing
sterility in the workspace.
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Beyond-use dating (BUD) for Compound Sterile Products (CSP) according to risk level:
(reference in pdf)
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Frequently Asked Questions: BUD vs Best Use
Why did my pharmacy say the IV bag had a “9 day beyond use date”
and in my recent IV class they told us to use the IV the same day it
was made?
• This is mixing the technical “use by date” the FDA and USP give a
particular product with the pharmacologic stability of the compound.
A great deal of information is given in the main document outlining
this confusing issue.
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How long can I keep a syringe or IV bag after
making it?
This answer has two very important parts which will be outlined
below:
1: BUD requirements for sterile compounds
2: Pharmacological stability of the constituents in the syringe or IV
bag
• The problem with a specific answer is that it cannot exclude one or
the other of these factors, and many times the advice given does just
that. The maximum time is defined by the level of risk the compound
carries but that time may be shortened by chemical and
pharmacologic stability factors.
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IV Stability?
• The issue with this factor in the question “How long can I keep a
syringe or IV bag after making it?” is that while the BUD criteria may
indicate storage of a medium-risk (appropriately compounded) sterile
product for 9 days under refrigeration (as an example) the
pharmacologic stability of that same mixture may degrade far sooner
than the 9 day “BUD rule” seems to indicate.
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IV Stability?
• The above being the case there does exist a separate but equally
important set of parameters which should be clinically considered in
IV nutrient bag preparation and storage. This clinical consideration is
degradation and dismutation of the additives in the bag. The import
of this portion is that while it may be technically acceptable to store
an admixture in an IV bag for the time periods specified the potency
of the nutrients in the admixture may not be maintained. This is why
various documents and instructors recommend various limits on the
time between compounding and use.
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IV Stability?
• This second issue of degradation and stability of additives is quite
complex in that each nutrient has completely separate stability
constants and when one adds them into an IV bag the interactions
can accelerate the loss of potency and dismutation.
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Risk Levels
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Risk Levels
No hood required:
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1A. Immediate use:
Unlike the other risk levels of CSPs, an ISO Class 5 environment is NOT
required for immediate-use preparations. Immediate-use preparations
are for emergency use or immediate patient administration (i.e.,
cardiac or respiratory arrest situation, emergency room or operating
room treatments, or any time where waiting for a low-risk prep would
put the patient at risk of harm because of delays in treatment).
Administration of immediate-use preps must commence within one
hour or less from the start of preparation. (Otherwise, they should be
discarded.) Only preparations that would otherwise be low-risk can be
considered immediate use.
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1A. Immediate use:
EXAMPLE: No more than three packages of sterile product can be
used, and not more than two entries into any one of the sterile
containers or packages can be made.
1. An IM B12 shot; B12+B100 shot or B12/B100/MgSO4 shot
2. An IV push of glutathione
3. An IV bag with two other vials / ampules used for additives
4. An immunization
5. Emergency med’s
6. Etc…
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Gowning in immediate use exemption:
Do healthcare practitioners preparing immediate use parenteral
products need to gown up, including gloves and mask?
• No. Immediate use compounding is exempt from all requirements of
the Chapter. That does not preclude the process of performing
scrupulous hand hygiene and adhering to appropriate proper aseptic
compounding technique.
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IV bag only and time limit?
If a commercially available IV fluid (i.e., Lactated Ringers or Normal
Saline) is spiked in anticipation of emergent administration, for
example in an ambulance, trauma emergency bay or a trauma OR
room, does the 1 hour expiration time apply to this situation?
• No. Since the spiking of an IV bag is not considered sterile
compounding, the one hour time limit would not be applicable. The
individual performing this task should use appropriate technique and
should perform (if possible) a thorough hand sanitization.
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Immediate Use Criteria:
http://www.snmmi.org/IssuesAdvocacy/content.aspx?ItemNumber=4907
• Immediate-use CSPs are used in those situations where there is a need for emergency or immediate patient administration
of a CSP.
• Immediate-use CSPs are not intended for storage for anticipated needs or batch compounding.
• Preparations that are medium-risk level and high-risk level CSPs shall not be prepared as immediate-use CSPs.
• The compounding process involves simple transfer of not more than three commercially manufactured packages of sterile
nonhazardous products or diagnostic radiopharmaceutical products from the manufacturers’ original containers and not
more than two entries into any one container or package (e.g., bag or vial) of sterile infusion solution or administration
container or device.
• During preparation, aseptic technique is followed and, if not immediately administered, the finished CSP is under
continuous supervision to minimize the potential for contact with nonsterile surfaces, introduction of particulate matter or
biological fluids, mix-ups with other CSPs, and direct contact of outside surfaces.
• Administration begins not later than 1 hour following the start of preparing the CSP.
• Unless immediately and completely administered by the person who prepared it, or immediate and complete
administration is witnessed by the preparer, the CSP shall bear a label listing patient identification information, the names
and amounts of all ingredients, the name or initials of the person who prepared the CSP, and the exact 1-hour beyond-use
date (BUD).
• If administration has not begun within 1 hour following the start of preparing the CSP, the CSP shall be promptly, properly,
and safely discarded.
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Risk Levels
With a hood but no buffer or ante area:
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1B: Low-Risk CSPs for Use Within 12 Hours
Under limited circumstances, sterile compounding may occur in a
segregated compounding area (such as a satellite pharmacy or
dedicated sterile compounding space) in which the ISO Class 5 PEC is
not located within an ISO Class 7 or 8 buffer area.
A segregated compounding area is a designated space, either a
demarcated area or room, in which compounding is restricted to
preparing low-risk, nonhazardous CSPs with a beyond-use time of no
more than 12 hours from the time of preparation.
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1B: Low-Risk CSPs for Use Within 12 Hours
All other requirements for low-risk CSPs must be followed, with the
exception that the ISO Class 5 PEC is not required to be located within
an ISO Class 7 buffer area.
The PEC must be separate from other operations, including sinks and
other water sources or drains, and away from unsealed windows or
doors that connect to high traffic areas, construction, warehouses, or
food preparation areas. Distinct labeling for conveying short BUDs
should be considered.
* Only syringes or IV bags prepared with a total of three or less sterile
products would fit this rule.
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Risk Levels
With proper buffer and ante areas around the
hood:
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1C: Low-risk CSPs
Low-risk CSPs must be compounded in an ISO Class 5 air quality
environment or better, from sterile ingredients, products, components,
and devices. No more than three packages of sterile product can be
used, and not more than two entries into any one of the sterile
containers or packages can be made.
* Only syringes or IV bags prepared with a total of three or less sterile
products would fit this rule.
FOR LOW RISK USE (1 “A, B & C” ABOVE) COMMON EXAMPLES INCLUDE:
• A syringe with one to three injection products added
• An IV bag with one or two injection products added (The IV bag, filled or not, counts as one sterile
product.)
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1D: Medium-risk preparations
Medium-risk preparations are compounded under the same conditions
as low-risk preps, with any one or more of the following conditions:
• Multiple individual or small doses of sterile products are combined or
pooled to make a prep that will be administered to multiple patients or
to one patient on multiple occasions
• Manipulations other than a single volume transfer are involved
• Unusually long duration of compounding process is involved
MEDIUM RISK EXAMPLES INCLUDE:
•
A syringe with four or more added injection products
•
Any IV bag with three or more additives
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1E: High risk
High risk: A high-risk sterile preparation is one where a non-sterile
product is included, so that the prep has to be sterilized.
Sterilization usually involves the use of filtering with a 0.2 or 0.22
micron filter within an ISO Class 5 environment. Filters of this size can
remove very small particles, like bacteria.
Steam and dry heat are other mechanisms of sterilization.
MOST all clinical compounding does NOT fall under High Risk.
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Do I need to comply with 503B, and what is it?
A 503B Facility is an Outsourcing Facility – so, no.
“The new law allows an entity that compounds sterile drugs to register as an
outsourcing facility. Once registered, an outsourcing facility must meet
certain conditions in order to be exempt from the FDCA’s approval
requirements and the requirement to label products with adequate
directions for use. Under the new law, the drugs must be compounded in
compliance with CGMP by or under the direct supervision of a licensed
pharmacist in a registered facility (section 503B(a)). The outsourcing facility
must also report specific information about the products that it compounds,
including a list of all of the products it compounded during the previous six
months, and information about the compounded products, such as the
source of the ingredients used to compound (section 503B(3)). In addition,
the outsourcing facility must meet other conditions described in the new
law, including reporting adverse events and labeling its compounded
products with certain information (section 503B(b)(5) and section
503B(a)(10)).”
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If installing a hood:
How to meet best practices and compliance:
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What are the rules for use of the hood and
the room it is in?
First, the environment created in order to maintain a cleanroom
environment is based on positive pressure.
Cleanrooms are designed to maintain positive pressure,
preventing "unclean" (contaminated) air from flowing inside and lessclean air from flowing into clean areas. The idea is to ensure that
filtered air always flows from cleanest to less-clean spaces.
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The Low to Medium Risk Product Compounding area has three environments to
meet current criteria; ISO Class-5 (the hood), ISO-7 (ante area), ISO Class-7 or 8
(buffer area) and ISO Class-9 “room air” (the rest of the lab or clinic)
Air flows from the hood outward: ISO-5 ISO-7 ISO-8  ISO-9
First Air  CSP  6” space  Hands  Ante area  Buffer area  Clinic
Hood=[“first air”] Product
6 inch space
Operators Hands / Edge
of Hood
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Operators
Body:
Buffer then
Ante areas
Your
clinic
45
Do you
need
this?
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Do you need
this?
No – not
unless doing
high risk
CSP’s
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Why are
these
things
out here?
AIRFLOW CLASS
5-7-8-9
GOALS FOR
THIS AREA??
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Why are these
things out
here? – AIR
TURBULANCE
AND DUST
Boxes and
other dusty
things outside
the ‘ante’
AIRFLOW CLASS
5-7-8-9
Store opened
materials from boxes
in their packages,
Hand prep, & gown glove here
GOALS FOR THIS AREA:
Minimal air disruption, reclean sterile gloves and
packages then place in hood
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From USP – latest edits
Line 1773 – 1777
Ante-area: An ISO Class 8 or cleaner area where personnel hand hygiene and
garbing procedures and other activities that generate high particulate levels
are performed. The ante-area is the transition area between the unclassified
area of the facility and the buffer area. [NOTE–The ante-area is sometimes
referred to as an ante-room when solid doors and walls are present.]
1792 – 1794
Buffer area: An ISO Class 7 (or ISO Class 8 if using an isolator) or cleaner area
where the PEC that generates and maintains an ISO Class 5 environment is
physically located.
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ISO-7 Air Source:
ISO=5 Hood
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Retrofit ISO Filters:
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Isolator Use: Avoiding ISO-7
• An isolator (“glove box”) may be used and avoid installation of an ISO7 air system.
• If used the air around the isolator must however be ISO-8 which still
requires an upgrade from typical “room air”.
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Avoiding ISO-7 ?
An isolator unit ‘may’
meet criteria to avoid
ISO-7 air. It must be
verified by the
manufacturer to meet
that requirement
however.
* And, a physical
buffer/ante system is
still required.
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A Brief Update on the FDA PCAC Actions and
our Testimony for Compounded Medications:
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Defense Last Month - Presentations to FDA’s
Pharmacy Compounding Advisory Committee
• Cesium Chloride
• Adequate defense refuting their claims of safety issues etc.
• Regardless of this the FDA recommendation to “not approve” upheld by PCAC
• Dichloroacetate
• Adequate defense refuting their claims of safety issues etc.
• Regardless of this the FDA recommendation to “not approve” upheld by PCAC
• DMPS
• Adequate defense including safety and use in acute arsenic poisoning
• Testimony (also corroborated by Ron McGuff and a respected Toxicologist) accepted
• PCAC OPPOSED FDA recommendation to “not approve” – recommended approval
Of note: THIS WAS NOT UNANIMOUS!
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Defense Last Month – FDA-PCAC Actions to date:
NOT APPROVED:
• acetyl-L-carnitine
• alanyl-L-glutamine
• Aloe Vera
• cesium chloride *(PCAC recommends Cat-2)
• chondroitin sulfate
• chrysin
• curcumin
• DCA *(PCAC recommends Cat-2)
• deoxy-D-glucose (2-DG)
• D-ribose
• Glycyrrhizin
• MSM
NOT APPROVED:
• rubidium
• domperidone
• germanium sesquioxide (On Cat-2)
• quinacrine hydrochloride
APPROVED:
• DMPS
• glutaraldehyde for topical use
• pyruvic acid for topical use
• tea tree oil
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Approach to PCAC Going Forward
Why Bother?
What the FDA – PCAC process
is NOT:
1. Basis for appeal – “best
evidence”
1. Safety
2. Efficacy
3. Difference from “FDA Approved”
medications
2. Collaboration
1. Other physician groups [?]
ACAM, A4M, AARM, ….
2. Compounding Pharmacy
Association
1.
2.
3.
4.
A “fair fight”
Logical
In service of “patient care”
Reasonable from the point of
view of integrative medicine
5. Able to be “swayed” by “just
the right argument!”
3. We must provide an opposing
view
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AANP Fundraising Site
https://www.youcaring.com/patientswhobenefitfromcompoundedmed
ications-687276
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Obviously we can’t cover all of this today:
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https://www.consultdranderson.com/product/oanp-web-call/
OANP Sponsored Webinar:
• Get to hear 3 hours of this in great detail
• Companion 27 page summary document of the rules etc.
• Many more stimulating slides and discussion
• Lots of VERY ANGRY questions from doctors
• All in all – a great time
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IV Therapy
Clinical Updates
Critical Thinking
Formula Sequencing
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Clinical Thinking: IV Therapy in Chronic Illness
The purpose of an IV approach to nutritional or botanical therapies is:
1. To gain access to the cells without GI interference
2. To infuse generally larger quantities of material than can be taken PO
3. To assist with repletion in significant disease states
4. To cause disease modification
5. And many others
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Clinical Thinking: IV Therapy in Chronic Illness
• In the past two decades I have used, observed and researched IV therapies
in the acutely and chronically ill patient population.
• My goal is to discuss patterns and improvements I have seen in general
nutrient and botanical IV therapies which I feel are improvements that can
positively affect patient outcomes.
• These observations are based on clinical response, pharmacologic research
and human subject outcomes.
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Clinical Thinking: IV Therapy in Chronic Illness
• Think mechanistically about agents
• Consider potential synergy
• Consider depth and intensity of disease state
• Formulate treatment plans incorporating synergy where
needed
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How Many Areas can the IV Effect?
8
Effectors:
1
7
5. Endocrine
1. Cell Function
2. Toxin
3. Biofilm
4. Immunology
2
6
7. Digestive – GI
Health
3
5
6. Psychosocial
8. Physical - Structural
4
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Main Mechanisms of Common IV Therapies
• Re-dox support agents:
• Glutathione
• Low dose IVC
• Nutrients
• ALA
• LAMC
• Phospholipids
• Chelation - Detox
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Main Mechanisms of Common IV Therapies
• Oxidative IV’s:
• High Dose IVC
• H2O2
• O3
• Artesunate + HDIVC
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Main Mechanisms of Common IV Therapies
• Cell membrane and Mitochondrial Support
• All Re-dox support agents generally
• Specifically:
• LAMC
• Low dose IVC
• ALA
• Amino Acid or like compounds (Taurine, Carnitine)
• Detoxification (chelation, curcumin…)
• Phospholipids
• Amino Acids
• Iron (if needed)
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Main Mechanisms of Common IV Therapies
• Biofilm Support:
•
•
•
•
Chelators
23 PPM Silver Hydrosol
Curcumin (?)
Not as potent as oral Rx
• Genomic IV support:
• Targeted nutrients for weak pathways:
• Histamine reduction, Sulfation, COMT-MAO, Methylation…
• Phase 1 & 2 supports
• Specific nutrient support for epigenetically weak areas:
• Immunoglobulin formation, Thyroid conversion, etc…
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Work up
and
Testing:
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Nothing you would not ordinarily provide in
the course of good medical management:
• Just because a patient is getting (or needs) IV therapy does not mean
you forget a proper work-up.
• Because of the possibility of electrolyte shifts and other comorbidities one should have appropriate foundational labs.
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Medical Work-up
• Comorbidities
• Concurrent / Prior treatment
• Prior response to IV therapy
• Screening labs
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Medical Work-up
• Comorbidities:
• For IV Tx the most important involve:
• Cardiovascular
• Renal
• Immune
• Concurrent / Prior Treatment:
• Other IV Tx
• Chemo
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Medical Work-up
• Prior response to IV therapy
• Anxiety
• Reactions / Allergy
• Access Issues
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Medical Work-up
• Screening labs
• Minimum:
• CBC+Diff+PLT
• CMP / Chem 14 (ALB/T.Prot/BUN/CRE/AlkPhos
Glucose/T.Bili/K/Ca/Cl/CO2/Na/ALT/AST)
• G6PD *(Oxidative therapies)
• Any other labs required to follow the patient and comorbidities.
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Formula
Customization
Basics
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Thought Process:
• What does the patient need?
• What nutrients or protocols may help?
• What schedule might work best?
• What testing is appropriate for work-up and follow-up?
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
Oral versus IV Nutrient dosing and GFR Dose adjustments:
• Dosing of oral nutrients can be limited by GI effects and absorption
(i.e. diarrhea from too much Magnesium or Vitamin C) whereas the IV
route can be a way of course around this limitation. While this
presents a benefit of the IV route over oral dosing it can also lead to
either overdosing or underutilization of the IV nutrient.
IV dosing of nutrients should consider at least the following five factors:
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
1. Deficiency state:
In a true deficiency state the patient may tolerate a
larger IV dose of a nutrient, yet administration of
cardio-active nutrients (Na, K, Ca, Mg…) should be
given at accepted safe rate and doses regardless of
need. Slight adjustments to this are often tolerated
such as a person with low Mg tolerating a greater
infusion dose of Mg – to their tolerance.
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
2. Tolerable IV dose of the nutrient / Patient tolerance:
In your course materials from IV classes you generally will find
data on “common IV doses” as well as “upper limits of dosing”
based on some research. Often the upper limits are not
needed for therapeutic use but give some comfort to the
prescriber in ordering a lesser dose. As an example the IV
dose tolerated of Taurine is many times over the typical or
necessary dose given in IVMT. Most common IV formulas are
well within these limits.
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
3. Frequency of IV’s:
This is important especially in the case of buildup of nutrients
– as an example one can give quite high Mg doses on one day
but overdose the patient the next day with the same dose
tolerated on day-1 simply due to the distribution kinetics of
Mg (see your IV class notes for the reason for this). Also trace
minerals can be given less frequently or in a finite series of IV’s
at a high dose (i.e. Zn can be given in a series in a deficient
person at over 25 mg per IV – but would never be given in
long term repeated IV’s at that dose without constant
monitoring of levels.)
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
4. Need for pharmacologic dose of a nutrient:
Again, breaking from the above if tolerated a particular
nutrient can be given at pharmacologic dosing for a
particular outcome (high dose IVC, Magnesium, certain
amino acids etc.)
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
5. GFR dose adjustments for IV nutrients:
This is often completely relative to the nutrient in question
and the volume of fluid used. Most water soluble nutrients
(the basis of most IVMT) are a strain on the kidney but only
at a lower level unless dosed quite high as a pharmacologic
dose (see above).
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General dose and administration guidelines as well as conversions
between estimated oral and parenteral doses.
Unpublished guideline Paul S. Anderson, ND – © 2013: Posted on the IV Nutrient Therapy Yahoo Chat Group July 2013
5. GFR dose adjustments for IV nutrients:
Some nutrients at very high dose (i.e. HDIVC) carry with them
a high Na load (again see your IV class notes) so they have to
be adjusted down if the GFR is compromised. Additionally if
one has a low GFR they may not tolerate the typical volume of
a high or isotonic IV fluid (see ‘fluid overload’ in your notes).
So one may for instance give a patient with CHF or Low GFR a
typical dose of B-Vitamins and Mg but in a lower fluid volume.
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Some considerations for IV additives:
• Common lab indicators for specific nutrients:
• Elevated GGT
• Glutathione and Magnesium augmentation
• Elevated AST/ALT
• B-6 and Magnesium
• Elevated HCYS / MCV
• Methylation support, B-6, Mg, Trace elements
• Decreased WBC
• Zinc, Germanium, Methyl support, Mg, Trace elements
• Decreased PLT
• Phosphatidylcholine
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Some considerations for IV additives:
• Intolerance of IV Magnesium
• Taurine, Glutathione
• Low RBC Magnesium
• Glutathione augmentation, Magnesium
• Sulfite reactions
• Molybdenum
• Post Chemotherapy / Radiation
• [Everything] – Hydration, Glutathione augmentation, Carnitine, Taurine,
Methylation and related support…
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Some considerations for IV additives:
• Underlying arrhythmias (especially atrial)
• Assure minerals (if available) are in chloride salt
forms and in balanced ratios
• Ca/Mg can range from 1:1 to 1:3
• Unless indicated K should be added only at a rate of
1-2 mEq / 250 mL base solution. (Many exceptions
but this is a safe peripheral parenteral dose.)
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Some considerations for IV additives:
• Inflammatory Bowel Diseases
• Mixed Amino Acid formulas
• Glutathione Augmentation
• Broad based nutrients
• Iron (where indicated)
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Some considerations for IV additives:
• If the patient has never had a nutrient IV then always start with a low
dose formula and watch for tolerance.
• If the solution is hyperosmolar and the patient cannot (or will not)
orally hydrate they may require 250-500 mL NS to hydrate them after
an IV (to avoid dehydration side effects)
• Remember: Once it is in the vein, you can’t take it back out!
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IV Sequencing
for
Optimal Efficacy
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Sequencing of IV’s: Clinically Proven Methods
• First rules:
1. There are no hard and fast rules – but generally one needs to work from the
“inside out” of the cell (and person).
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Sequencing of IV’s: Clinically Proven Methods
• First rules:
2. Generally as you improve function in the weakest area you may have to
interrupt your therapy plan and re-assess.
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Sequencing of IV’s: Clinically Proven Methods
• First rules:
3. In most cases use water soluble agents first and then later
phospholipids and lipophilic agents.
o Many react badly to lipids put into an inflamed system.
o CRP, other markers and pain can rise due to inflammatory lipid displacement
o Many react badly to lipids infused prior to mitochondrial repair.
o Phospholipid negative reaction is NOT a sign of treatment failure but
rather need to reorganize therapies.
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Working from the “inside out”:
1. Mitochondria
1.
2.
3.
Water sol. Nutrients
Iron
Curcumin (‘chelates’)
Cell Membrane
Cytosol
2. Cytosolic processes
1.
2.
Water sol. nutrients
GSH
Mitochondria
3. Membranes
1.
2.
Phospholipids
Chelation
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Sequencing of IV’s: Clinically Proven Methods
• First rules:
4. Never detox a weak patient. Build them up first.
o Detox and Chelation are very metabolically demanding
o They require cell support first and lots of antioxidant support
o They also trigger biofilm breakdown!
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Sequencing of IV’s: Clinically Proven Methods
• First rules:
5. Make sure to manage expectations in the IV (and any) patient. Just because
your first ten tries with IV glutathione were magical, #11 may prove to be
seemingly a non or bad reactor.
o There are always reasons for reactions!
o You can always re-assess and re set plans
o If you tell the patient this up front it is more accepted when it happens
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Sequencing of IV’s: Clinically Proven Methods
If tolerated, a synergy (on the same day) can be gained in advanced
complicated cases by this sequence:
1. Water soluble nutrients
2. Glutathione
3. LAMC (Poly) or ALA
4. Curcumin (low dose) / Artesunate (see below)…
5. Phospholipids
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Sequencing of IV’s: Clinically Proven Methods
• In a patient with active biofilm therapy one can consider:
1. Use of chelation IV or Biofilm PO addition
2. Anti-infective IV
3. If needed any other IV that will not react with the Anti-infective or
chelation agents
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Sequencing of IV’s: Clinically Proven Methods
In most patients where the stress of too many IV’s on one day one can
consider:
1. Alternating therapies based on MOA of the IV’s – keeping the MOA’s that
are synergistic on the same day but alternating differing MOA’s on different
days. i.e.
• ART-HDIVC Monday and Friday
• Nutrients – GSH – LAMC (Poly-MVA) Wednesday
* See the online - IV THERAPY COMPATIBILITY CHART:
https://www.academia.edu/21926047/IV_Therapy_Use_and_Compatibility_Chart_-Prepared_for_Anderson_Medical_Group_BCRC_and_SCRI_All_rights_reserved
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Frequency and Timing of IV’s in the
chronically ill:
• Acute cases are much more limited and simple
• Chronic cases consider:
• One to three IV treatments per week for at least four to eight weeks.
• Then if progressing run a slow withdrawal trial:
• Decrease 2X a week IV’s to 1X a week for a month then 1X every 2 weeks etc…
• If they relapse increase frequency.
• I generally tell chronically ill patients we will not know fully if a therapy is working for
10-20 IV sessions.
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Some Fundamentals for IV Botanicals:
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Glycyrrhizin
• Anti-viral, Hepato-protective
• Very safe
• Always test but weekly IV’s usually do not affect BP
• Mixes in most all water soluble IV’s (Vitamin or Mineral):
• IVC, Vit-Min IV’s…
• Generally dosing needs to match disease:
• Hep-C and HIV studies used 120-240 mg
• General liver support 40-80 mg
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Curcumin
• Low dose uses (500 mg or under):
• Anti-inflammatory
• Chelation support (CNS and Mitochondrial)
• Follow the dilution and admin rates in the monograph (link below)
• Generally easier IV than high dose
• Usually we use 100-300 mg
• High dose uses (10-40 mg/kg):
• Oncology
• Follow the dilution and admin rates in the monograph (link below)
• Very tight administration guidelines
• High cost IV’s
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Artesunate
• Two major use areas based on the two major MOA (see Monograph
below):
• Oxidative support:
• Best prior to an oxidant IV (HDIVC)
• Doses 60-300 mg (much higher is safe but not affordable)
• Think of in Acute and Chronic Infections & Cancer
• Immune modulation support:
•
•
•
•
•
ART has immunomodulatory effects similar to Curcumin and other botanicals
I use in autoimmunity and complex cases where infection and autoimmunity co-exist
ART can be given without an oxidative IV
Still best in its own bag, but can be in series as in the above slides
60-300 mg average doses
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Some Reminders:
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IV Solutions with “Special Handling” Required
• Vit-D (Calcitriol) – No other Vit-D form is IV
–Infused ALONE –
• Preferably in a non-ionic (D5W) solution.
• Also tolerates plain NS as a carrier.
–High potential for DIC, Microemboli, Kidney damage etc
when added to other infusates.
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IV Solutions with “Special Handling” Required
• Alpha-lipoic Acid / ALA – OR – LAMC (PolyMVA)
–Infused ALONE –
• Preferably in D5W or NS (ask your pharmacy).
–High potential for DIC, Microemboli, Kidney
damage etc when added to other infusates.
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IV Solutions with “Special Handling” Required
• Phosphatidyl-choline / PTC
–Infused ALONE –
• Mixed in a non-ionic (D5W) solution.
–High potential for phlebitis, DIC, Microemboli, Kidney
damage etc when added to other infusates.
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IV Solutions with “Special Handling” Required
• ALA
• PTC
• Vit-D (Calcitriol)
• Poly-MVA
• Curcumin
• Etc…
• All of these require either a line change or a line flush between their
infusion and any prior or successive IV bag or push.
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IV Solutions with “Special Handling” Required
• Glutathione / GSH :
–Compounded in the reduced state.
–MDV should be stored under refrigeration.
–Infuse as a separate push or in it’s own small bag
–This keeps the Reduced GSH from becoming
oxidized by other IV constituents.
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IV Solutions with “Special Handling” Required
• Artesunate:
–Supplies in a ‘dry’ lyophilized form.
–Reconstitute ONLY as recommended by the
pharmacy who manufactured it.
–Infuse as a separate push or in it’s own small bag
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So, what can I use on the same day as
another IV?
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“The Chart”
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Links to monographs!
• GLUTATHIONE AUGMENTATION
https://www.academia.edu/21925456/Glutathione_Augmentation_in_a_ne
rve_injury_model
• IV THERAPY COMPATIBILITY CHART
https://www.academia.edu/21926047/IV_Therapy_Use_and_Compatibility
_Chart_Prepared_for_Anderson_Medical_Group_BCRC_and_SCRI_All_rights_reserv
ed
• ASCORBATE FORMULAS AND ELECTROLYTE RESEARCH
https://www.academia.edu/13255726/IV_Ascorbate_and_Electrolytes
• ASCORBATE AND ONCOLOGIC THERAPIES
https://www.academia.edu/10024397/Ascorbate_and_Oncologic_Therapies__Research_Review
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Links to monographs!
• MTHFR IN THE CFS-FMS POPULATION
https://www.academia.edu/11813721/MTHFR_in_the_CFSFMS_Patient_Population_Incidence_and_therapy
• ARTESUNATE:
https://www.academia.edu/20316500/Artesunate_Monograph
• CURCUMIN:
https://www.academia.edu/20316553/Curcumin_IV_Use_Monograph
• LAMC (PolyMVA):
https://www.academia.edu/20316600/Lipoic_Acid_Mineral_Complex_P
olyMVA_Monograph
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Other Resources:
• Other Documents, Webinars etc.:
www.ConsultDrA.com
• AAMP Conferences (my new “Treat the Whole Person”
series):
https://aampconferences.com/
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Thank you!
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