Download Droxanol - nadurel pharma

Natural Pain Medica/ons Nadurel Pharma Inc November , 2012 © CuraPhyte Technologies Inc Droxanol •  Drug Class: –  NSAID / COX inhibitor •  Key clinical advantage : –  Safety profile: no side effects typical of a conven/onal COX inhibitor* * Not observed in more than 20 clinical trials and post-­‐marke7ng surveillance. © CuraPhyte Technologies Inc Pavosic •  Drug Class: –  Opioid & 5-­‐HT1A + 5-­‐HT7 –  Analgesic + HypnoIc/sedaIve •  Key clinical advantage: –  Safety profile: •  No addic/on/physical dependence •  High tolerability versus conven/onal narco/cs. © CuraPhyte Technologies Inc Plant Tradi/onal Medicine Devil’s claw (Harpagophytum procumbens) •  South African plant recognized for its anI-­‐inflammatory properIes. •  AcIve part of the plant is the dried secondary roots. •  An anI-­‐inflammatory, anIrheumaIc and analgesic remedy. •  Doses* range from 0.6 to 9 grams of the dried root daily (or the equivalent in the form of a dried extract). Droxanol:
Equivalent to 3744 mg dried root per tablet (23.4 mg harpagoside per tablet)
* Doses considered safe by regulatory agencies around the world. © CuraPhyte Technologies Inc Plant Tradi/onal Medicine Devil’s claw (Harpagophytum procumbens) •  The iridoid glycoside, harpagoside, linked to its anI-­‐inflammatory and analgesic benefits. •  PD & PK -­‐ 3 studies in human volunteers*: –  RelaIon between serum harpagoside levels and the inhibiIon of leukotriene biosynthesis. –  Maximum levels of plasma harpagoside reached a\er 1.3 to 2.5 hours. •  A linear relaIonship between dose and the first maximal concentraIon (Cmax) or area under the curve (AUC). –  Harpagoside eliminaIon half-­‐life has been reported as 5.6 hours. * Clin Pharmacol Ther. 2001 May;69(5):356-­‐64. © CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Enteric coa/ng required: –  Studies demonstrated loss of anI-­‐inflammatory effects by oral administraIon –  Dose-­‐dependent effects observed with intraperitoneal and intraduodenal administraIon –  Enteric coaIng -­‐ protecIon of efficacy demonstrated –  Droxanol has an enteric coa/ng that conforms to USP standards. © CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) InhibiIon of Cyclo Oxygenase 2 Assists the extracellular matrix construcIon (synthesis of GAGs) Synthesis of hyaluronic acid (human chondrocytes) Iridoids (harpagosides) interact with Arachidonic Acid metabolism pathways:
• Action on eicosanoids synthesis
• Action on cyclo-oxygenase, lipoxygenase and NO synthetase
• Action on TNFa liberation
• Action on Cys-LT synthetis
• Action on enzymes responsible for collagen degradation
© CuraPhyte Technologies Inc Manufacturer’s in-house data.
Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Over 23 clinical trials in patients with OA, RA or low back pain.
Double-blind-RCT: 6 trials
–  Articular pain; 2 g root/day (n=89; 2 mnths Rx)
–  Knee or hip OA (n=122; 4 mnths Rx)
–  Active Controlled: Harpadol (2.6 g/day) vs 100 mg Diacerhein - knee or hip OA
(n=122; 4 mnths Rx)
–  Active Controlled: Doloteffin (60 mg harpagoside/day) vs 12.5 mg Vioxx - low back
pain (n=44; 6 wks Rx)
–  Pain of back, shoulder & neck (n=63; 4 wks Rx)
–  Active Controlled: phenybutazone (300mg/day D1-4; 200mg/day D5-28) (n=50; 28
days Rx)
Placebo-RCT: 7 trials
– 
– 
– 
– 
1 trial: osteoarthritis (n=46; 20 wks Rx)
1 trial: arthritis (n=50; 3 wks Rx)
2 trials: low back (n=197 & 118; 4 wks Rx)
3 trials: rheumatic conditions (n=100 each; 30-days Rx)
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) –  Observational post-marketing trial: 4 trials
•  N=250 (104-low back, 85 knee OA, 61 hip OA); 8wks Rx
•  N=675 (OA, spondylarthropathies, fibromyalgic); 8wks Rx
•  N=630 arthritis conditions; 6mnths Rx
•  N=13 arthritic symptoms; 6wks Rx
–  Uncontrolled –Open-label trial: 3 trials+
•  75 patients – hip, knee OA -12-weeks
•  130 patients – chronic back – 6-months
•  102 patients – acute low back - 6-months
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  According to UpToDate (www.uptodate.com): –  "Devil's claw reportedly improves joint mobility and reduces pain and swelling in arthriIs." –  "It may be more effecIve for osteoarthriIs as compared to rheumatoid arthriIs." –  "It may be more effecIve for chronic, rather than acute, arthriIs symptoms." *UpToDate® is an evidence-­‐based clinical decision support system authored by physicians © CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  "There is a growing body of scien7fic evidence sugges7ng that devil's claw is safe and beneficial in the short-­‐term management of pain related to degenera7ve joint disease or osteoarthri7s. It may be equally effec*ve as drug therapies, such as non-­‐
steroidal an7 inflammatory drugs (or may allow for dose reduc*ons or cessa*on of these drugs in some pa7ents).“ – Natural Standard database* *Natural Standard is imparIal; not supported by any interest group, professional organizaIon or product manufacturer. © CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Double-blind, randomized, multicentre clinical study:
–  Harpadol (6 capsules/day; 2610 mg/day). Droxanol:
Equivalent to 3744
•  9.5mg harpagoside/capsule (57 mg/day). mg dried root per
tablet
(23.4
mg
•  435 mg powdered cryoground Harpagophytum
harpagoside
per
tablet)
procumbens.
–  Diacerhein 100 mg/day
–  Rx 4 months; 122 patients OA knee and hip.
–  Evaluations:
•  pain & functional disability: 10 cm horizontal VAS.
•  severity of OA: Lequesne's index.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Double-blind, randomized, multicentre clinical study (contd):
–  Results:
•  Spontaneous pain = significant improvement; no
difference between groups.
•  Progressive & significant ↓ Lequesne functional index; no
statistical difference.
•  End of trial:
–  Harpadol significantly less NSAIDs and antalgic drugs.
–  Frequency of AE was significantly lower in Harpadol
group.
–  Most frequent AE = diarrhea, occurring in 8.1% and
26.7% of Harpadol and diacerhein patients
respectively.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) Droxanol:
•  Double-blind clinical study:
Equivalent to 3744
–  89 patients with articular pain received 670mg of
mg dried root per
devil's claw three times daily (total of 2010 mg dried tablet (23.4 mg
root) for 2 months.
harpagoside
per
tablet)
–  Results:
•  Significant decrease in severity of pain and a
significant increase in spinal and cofexomoral
mobility in the experimental group.
•  No side effects or changes in safety parameters
were observed.
–  Lecomte A and Costa JP. Harpagophytum dans l'arthrose: Etude en double insu contre placebo. Le Magazine 1992;15:27-­‐30.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Placebo-controlled clinical study:
–  50 arthriIc paIents receiving devil's claw, two capsules of 400mg three Imes daily for 3 weeks –  StaIsIcally significant decrease in severity of pain was measured, with more frequent improvements in moderate cases compared to more severe cases. –  Guyader M. Les plantes anIrhumaIsmales. Etude historique et pharmacologique, et etude clinique du nebulisat d'Harpagohytum procumbens DC chez 50 paIents arthrosiques suivis en service hospitalier [DissertaIon]. Universite Pierre et Marie Curie, 1984.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  20-week, Randomized, Placebo controlled study: Droxanol:
–  46 patients with OA hip.
–  Two tablets per day (extract equivalent to
2400 mg dried root, or placebo tablets.
–  Both groups also received identical, stepwise-reduced
daily doses of ibuprofen: 800mg daily for the first 8
weeks, 400mg daily for a further 8 weeks, and none
during the last four weeks of the study.
–  Efficacy: WOMAC index.
–  Frerick H, Biller A, and Schmidt U. Stufenschema bei Coxarthrose. Der Kassenarzt 2001;5(34):41.
© CuraPhyte Technologies Inc Equivalent to 3744
mg dried root per
tablet
(23.4
mg
harpagoside
per
tablet)
Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  20-week, Randomized, Placebo controlled study (contd):
–  WOMAC:
•  Scores decreased in both groups over the study period, despite
the reduced dose of ibuprofen.
•  Sub-scores for stiffness, pain and dysfunction decreased
similarly in both groups.
–  In final ibuprofen-free period:
•  Increase of 20% or less in the pain score was considered a
clinically relevant response rate:
–  71% of devil's claw patients
–  41% of placebo patients (p=0.04).
•  52% of patients in the devil's claw group, compared to 36% in
the placebo group, were able to complete the study without
using rescue therapy during the ibuprofen-free period.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Randomized, Placebo controlled clinical study:
–  100 paIents suffering from various rheumaIc pain Droxanol:
syndromes Equivalent to 3744
–  2460mg Harpagophytum extract (equivalent to mg dried root per
4920 mg dried root (30mg harpagoside) per day) or tablet (23.4 mg
harpagoside
per
placebo. tablet)
–  Aber 30 days: •  Number of paIents with moderate pain: –  6 in Harpag group and 32 in the placebo group. •  Only 1 in Harpag group with severe pain vs 9 in placebo. •  AE 2 paIents (harpag group: diarrhea; placebo: mild gastriIs).
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) Droxanol:
•  Observational postmarketing study:
Equivalent to 3744
–  Total of 250 patients enrolled (227 completed):
mg dried root per
•  104 patients low back pain
tablet
(23.4
mg
harpagoside
per
•  85 patients arthritic knee pain
tablet)
•  61 patients arthritic hip pain
–  Doloteffin® (60mg harpagoside) daily for 8 weeks.
–  Outcome measures:
•  Arhus low back pain index,
•  WOMAC index,
•  German version of the HAQ,
•  Unvalidated measures (total pain index, three score index,
the patient's global assessment of the effectiveness of
treatment).
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Observational postmarketing study (contd):
•  Multivariable analysis results:
–  Improvement greater when the initial pain and disability score was high.
–  older patients improved less than younger,
–  Hip group improved more than back group,
–  Improvement in knee group less readily differentiated from back group.
–  Patients with back pain who required NSAIDs during the 8 weeks:
•  used significantly more NSAIDs per patient than patients in the
other two groups, but that requirement also declined more with
time.
–  About 10% of the patients suffered from minor AE possibly attributable
to Doloteffin.
–  Between 50% and 70% of the patients benefitted from Doloteffin with
few adverse effects (primarily gastrointestinal).
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) Droxanol:
•  8-Week Open-Label study:
Equivalent to 3744
–  130 paIents non-­‐radiaIng chronic back pain (>6 months) mg dried root per
–  480mg of devil's claw root dry extract BID (equivalent 4800 mg tablet
(23.4
mg
dry root daily). harpagoside
per
tablet)
–  Rescue medicaIon (paracetamol) available 1st 4 weeks. –  Results: •  MulI-­‐dimensional pain scale and the Arhus back pain index decreased significantly (p<0.001) during treatment. •  The mobility of the spinal column, determined by the average finger-­‐to-­‐floor distance and using Schober's sign, also improved significantly (p<0.001). •  First subscale of Clinical Global Impression decreased from 4.6 to 2.9 a\er 8 weeks of treatment. –  Laudahn, D. and Walper, A. Efficacy and tolerance of Harpagophytum extract LI 174 in pa*ents with chronic non-­‐radicular back pain. Phytother.Res. 2001;15(7):621-­‐624.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Equivalence study comparing 2 doses vs placebo:
–  N= 197 patients,
Droxanol:
–  N=65: 200mg H600 tablets TID for 4 weeks (equivalent Equivalent to 3744
mg dried root per
to 18.4 mg harpagoside per tablet);
tablet
(23.4
mg
harpagoside
per
–  N=66: 400mg H1200 tablets TID for 4 weeks
tablet)
(equivalent to 37.2 mg harpagoside per tablet);
–  66 received placebo.
–  Principal outcome:
•  Number of patients who were pain-free (without
the permitted NSAID) for 5 days at the end of the
trial.
–  Other outcome measures:
•  Arhus low back pain index relative to baseline and
consumption of rescue medication (Tramadol®).
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Equivalence study comparing 2 doses vs placebo (contd):
–  Results:
–  Pain-free patients =:
•  9% H600 group
•  15% H1200 group
•  5% for placebo (p=0.027).
–  Overall median Arhus index scores:
•  decreased from 55% at baseline to 20% by week 4, but
there was no statistically significant difference between
both treatment groups and the placebo group.
© CuraPhyte Technologies Inc Plant Scien/fic Evidence Devil’s claw (Harpagophytum procumbens) •  Postmarketing study:
–  N = 675 patients with painful OA, spondylarthropathies or fibromyalgic
complaints.
–  Treated daily for 8 weeks with 480mg BID of a devil's claw root dry extract.
–  Measured outcomes:
•  CGI score, reduction in symptom severity score, and use of NSAIDs or corticosteroids as
co-medications.
–  Results:
•  CGI scores was rated good or very good in 82% of cases.
•  Symptom score for painful motion decreased by 53% from 2.23
(indicating moderate pain) to 1.04 (indicating slight pain) after 8 weeks.
•  Co-medication doses were reduced or discontinued in 60% of the 464
patients taking NSAIDs and 56% of the 50 patients taking
corticosteroids.
–  Ribbat JM and Schakau D. Behandluing chronisch ak*vierter Schmerzen am Bewegungsapparat. NaturaMed 2001;16:23-­‐30.
© CuraPhyte Technologies Inc AE Profile Devil’s claw (Harpagophytum procumbens) •  General:
–  Known allergy/hypersensitivity to Devil's claw. Some of AE
may be attributable to allergic rather than dose-dependent
effects.
•  Gastrointestinal:
–  Mild gastrointestinal upset, diarrhea, anorexia, or loss of
taste, especially at high doses.
•  Cardiovascular:
–  Use cautiously in patients with heart disease, especially
patients with arrhythmias or taking antiarrhythmic agents, due
to potential negative inotropic effects of devil's claw. In
rabbits, devil's claw has been associated with negative
chronotropic, as well as positive and negative inotropic
effects. However, these effects have not been clearly
documented in humans.
© CuraPhyte Technologies Inc Recommended Use & Contraindica/ons Devil’s claw (Harpagophytum procumbens) •  INDICATIONS AND CLINICAL USE
–  Droxanol™ is a natural NSAID with COX-2
inhibition. It is indicated for the treatment of
acute and chronic pain.
–  Use 1 tablet (3.74 g dried root) of
Droxanol twice a day (morning and
evening).
•  Optimal dosing frequency: TID.
•  Drug Interactions:
–  No cytochrome P450 induction or inhibition.
•  CONTRAINDICATIONS:
–  Do not use during pregnancy. Lack of
evidence to recommend safe use. © CuraPhyte Technologies Inc Droxanol:
Equivalent to 3744
mg dried root per
tablet
(23.4
mg
harpagoside
per
tablet).
T1/2 = 5.6 hrs.
Droxanol™ -­‐ Pharmaceu/cal Quality •  QC of herb raw material: –  Naturex – supplier high quality extracts –  Species, subspecies idenIficaIon –  QuanIficaIon of harpagosides. –  Purity: •  pes7cides, heavy metals, microbiology, solvent residues •  QC release of finished product: –  Enteric coaIng disintegraIon tesIng –  Purity: heavy metals, microbiology •  Standardized harpagoside content for lot-­‐to-­‐lot consistency © CuraPhyte Technologies Inc Plant Tradi/onal Medicine California poppy (Eschscholzia californica) •  TradiIonally used in North America for its analgesic, hypnoIc and sedaIve properIes. •  AcIve part of the plant: dried aerial parts (herb top). •  There is no known dependence or addicIon. –  Not classified as a narco/c or controlled drug. •  Trials with herb: –  Tested at significantly lower doses (200 mg dried herb top/day) in a DoubleBlind, Randomized Clinical Trial in paIents with depression (DSM-­‐III-­‐R); 3mnths Rx. Pavosic:
–  2 Pilot studies: acute & chronic pain. –  1 ongoing trial as co-­‐analgesic. © CuraPhyte Technologies Inc Equivalent to 3000 mg
dried herb top per capsule
(0.8%
isoquinoline
alkaloids per capsule).
Plant Scien/fic Evidence California poppy (Eschscholzia californica) •  3 key alkaloids: –  0.8% Isoquinoline alkaloids: •  Californidine (60.0 -­‐ 80.0 % of total alkaloids by HPLC) •  Escholtzine (10.0 -­‐ 30.0 % of total alkaloids by HPLC) •  Protopine (3.0 -­‐ 10.0 % of total alkaloids by HPLC) Pavosic:
Equivalent to 3000 mg dried herb top per capsule (0.8% isoquinoline
alkaloids per capsule).
© CuraPhyte Technologies Inc Plant Scien/fic Evidence California poppy (Eschscholzia californica) •  Pharmacological proper/es demonstrated : –  Opioid & 5-­‐HT1A & 5-­‐HT7 serotonin acIvity –  Seda/ve effects using a benzodiazepine receptor antagonist. –  Anxioly/c effects using a benzodiazepine receptor antagonist. –  No anIconvulsant or myorelaxant effects. –  No an/cholinergic effects. –  A dose-­‐response effect observed for peripheral analgesia. © CuraPhyte Technologies Inc AE Profile California poppy (Eschscholzia californica) •  Drowsiness: frequently reported by patients taking alcohol or other
sedatives/tranquilizers.
•  Hypotension: A single report of hypotensive effect in an elderly
bedridden patient taking multiple medications including hypertension,
antinausea and analgesic drugs.
•  Insomnia: low incidence but is known to occur in some patients.
•  Altered Dreaming: frequently reported by patients as pleasant or
strange dreams.
•  NO REPORTS OF: hallucinations, euphoria, constipation,
physical dependence/addiction.
© CuraPhyte Technologies Inc Opioid side effects (only those is red observed with Pavosic) The other side effects of opioid narcotics range from
abnormal
dreams,
agitation,
aggression,
apprehension, attention disturbances, impaired
coordination,
depression,
confusion,
cognitive
disorder, dizziness, drowsiness, dysphoria, euphoria,
hallucinations,
headache,
insomnia,
physical
dependence, memory impairment, mood alterations,
nervousness, panic attacks, etc.
Dose-­‐Dependent AEs: Respiratory depression, decreased cerebral blood flow, miosis, consIpaIon, tolerance, physical dependence, overdose leading to death from respiratory arrest. © CuraPhyte Technologies Inc Recommended Use & Contraindica/ons California poppy (Eschscholzia californica) •  INDICATIONS AND CLINICAL USE –  Pavosic™ is indicated for the treatment of pain (analgesic) and/or the treatment of insomnia. –  Use 1 capsule (3000 mg dried herb top) of Pavosic™ at night as an analgesic/seda/ve. •  Poten/al Drug Interac/ons –  Pavosic™ may have an addiIve effect when used with sedaIves, tranquilizers, hypnoIcs and analgesics. •  Contraindica/on: –  Do not use in pregnant women.
© CuraPhyte Technologies Inc Pavosic™ -­‐ Pharmaceu/cal Quality •  QC of herb raw material: –  Naturex – supplier high quality extracts –  Species, subspecies idenIficaIon –  QuanIficaIon of isoquinoline alkaloids (3 specific). –  Purity: •  pes7cides, heavy metals, microbiology, solvent residues •  QC release of finished product: –  Quan/fica/on: isoquinoline alkaloids (3 specific) –  Purity: heavy metals, microbiology •  Standardized isoquinoline alkaloid content for lot-­‐
to-­‐lot consistency © CuraPhyte Technologies Inc Physician Case Studies -­‐ Pavosic TYPE OF PAIN
CO-MEDICINE
TREATMENT WITH
OUTCOME POST RX
Cervical-chronic + insomnia
Tylenol, Advil
Patient can sleep; complete pain relief.
Cervical-chronic + insomnia
Tylenol, Advil
Patient can sleep; complete pain relief.
Disc hernia –chronic +
anxiety + insomnia
Nothing
Patient can sleep; complete pain relief
Arthritis-chronic + insomnia
Unknown
Too much sedation after 2-3 days of treatmentswitched to morning
Fibromyalgia-chronic +
insomnia
Lyrica
Kept patient awake therefore switched to morning
Fibromyalgia-chronic
Lyrica
Kept patient awake therefore switched to morning;
pain relief
Fibromyalgia-chronic +
insomnia
Lyrica, Tylenol
Patient can sleep
OA-chronic
Multiple NSAIDs,
Tylenol
Empracet caused sedation + did not relieve pain.
Switched to herb BID: no sedation + pain relief
Car accident: back, neck
chronic pain
Diclofenac
Complete pain relief; no sedation; taken BID
Surgical knee prosthesis
implant
Morphine morning
+
Patient Ican
© CuraPhyte Technologies nc sleep + pain relief
Pavosic evening
Integra/ng Natural Medica/ons Droxanol •  Drug Class: –  NSAID –  COX inhibiIon + other targets •  Main advantage vs convenIonal NSAIDs: –  Safety profile: •  no GIT irritaIon, no renal toxicity, no cardiovascular toxicity. •  Consider if paIent needs NSAID but convenIonal NSAID is contraindicated. •  No cytochrome P4503A4 contraindicaIon. © CuraPhyte Technologies Inc Integra/ng Natural Medica/ons Pavosic •  Drug Class: –  Opioid & 5-­‐HT1A + 5-­‐HT7 –  HypnoIc/sedaIve •  Main advantage vs convenIonal opioids: –  No addic/on/physical dependence + high tolerability. •  Consider if paIent needs further analgesia or has night pain. •  No contraindicaIon for use with NSAID, acetaminophen, Lyrica, hydromorphone. •  No cytochrome P4503A4 contraindicaIon at 1q & bid. © CuraPhyte Technologies Inc Natural Meds interven/on Ini/al Pharmacological interven/on Night Pain NSAID contraindicated Examples of Analgesic Choices acetaminophen
ibuprofen celecoxib 500 mg q 4 hrs po
MDD 4000 mg 400 mg q 4-­‐6 hrs po MDD 3200 mg 100 mg po bid
MDD 400 mg Natural Meds Droxanol Pavosic 3.74 gram (468 mg extract) po bid 3 gram (600 mg extract) at night Reassessment? Second Pharmacological interven/on. Upward /tra/on? Need co-­‐analgesic-­‐-­‐adjuvant meds? © CuraPhyte Technologies Inc Relief obtained Second Pharmacological interven/on -­‐ Reassessment ↑ Analgesia + minimize adverse effects Need hypno/c/seda/on for insomnia? Co-­‐analgesic—adjuvant use Clinical advantage: No physical dependence & Safety/tolerability Non-opioid analgesics (acetaminophen, NSAIDs, COX-2 Inhibitors);
Tramadol;
Opioids;
Alpha 2 adrenergic agonists;
Antidepressants (tricyclics and SNRIs);
Antiepileptic drugs (gabapentin, pregabalin);
Muscle relaxants;
N-methyl-d-aspartate (NMDA) receptor antagonists;
Topical analgesic agents
+ Upward /tra/on? Need co-­‐analgesic-­‐-­‐adjuvant meds? Co-­‐Analgesic/Adjuvant Natural Meds Droxanol
Pavosic 3.74 gram (468 mg extract) po bid 3 gram (600 mg extract) at night Droxanol = NSAID with COX-­‐2 inhibi/on; Pavosic = opioid/serotonin mechanism (analgesic +hypno/c) © CuraPhyte Technologies Inc