![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 33. This is the beginning of the thread.
Posted by dbc on February 16, 2007, at 16:34:13
SIDE EFFECTS
As with many medications, there can be side effects.
This risk must be balanced with the medical need. Most patients find the benefits outweigh the risks. All people taking medicines have some risk of becoming dependent on the medicine. Consult your doctor about how this may affect you.
Adverse events may include:* Mood changes
* Muscle strain
* Extraordinary thinking
* Dermal gloss
* Impulsivity induced consumption
* Excessive salivation
* Hair growth
* Co-dependency with inanimate objects
* Markedly delayed sexual climax
* Inter-species communication
* Taste perversion
* Terminal smile
* Oral inflammation
* Very rarely users may experience a need to change physicians.
Posted by Quintal on February 16, 2007, at 17:43:50
In reply to Havidol, a revolution in psychiatric medicine!, posted by dbc on February 16, 2007, at 16:34:13
http://www.havidol.com/zing.html
It's brilliant! I couldn't have put it better myself. Modern psychopharmacology in a nutshell.
http://www.havidol.com/score.php
Oh dear! It seems I'm having a massive DSACDAD attack............. off to ER to get an emergency script for avafynetyme........
Q
Posted by linkadge on February 16, 2007, at 18:29:22
In reply to Take the DSACDAD online diagnostic test, posted by Quintal on February 16, 2007, at 17:43:50
Oh dear.
How horrable. That site is very extensive.
Linkadge
Posted by linkadge on February 16, 2007, at 18:32:07
In reply to Re: Take the DSACDAD online diagnostic test, posted by linkadge on February 16, 2007, at 18:29:22
Who creates a page like this? This would have taken quite some time.
Linkadge
Posted by Quintal on February 16, 2007, at 19:56:09
In reply to Re: Take the DSACDAD online diagnostic test, posted by linkadge on February 16, 2007, at 18:32:07
>Who creates a page like this? This would have taken quite some time.
I wondered the exact same thing. It actually had me fooled for a few seconds, it's so very much like those pages for Lunesta and Rozerem and their ilk. Someone disgruntled social phobe who happens to be very clear sighted most likely. Accusations of scientology will most likely abound from certain quarters.
Q
Posted by Quintal on February 16, 2007, at 20:11:36
In reply to Havidol, a revolution in psychiatric medicine!, posted by dbc on February 16, 2007, at 16:34:13
Q: How do I get help for DSACDAD?
A: The first step is to talk with your doctor. Explain the symptoms you've been experiencing. The doctor may recommend a physical checkup to determine whether there is an underlying physical reason for your symptoms. Your physician may make a referral to a qualified mental health professional, such as a psychiatrist, psychologist, social worker, or counselor. You should then make your doctor aware of DSACDAD. If DSACDAD is diagnosed you should ask your doctor about HAVIDOL - the first and only treatment for DSACDAD. Only your doctor or a psychiatrist can prescribe HAVIDOL.
Q: I have been prescribed HAVIDOL 20 mg, how should I take it?
A: HAVIDOL can be taken at any time of day. HAVIDOL is available in tablets or suppositories, depending on your preference. It is recommended that suppositories be used at night.
Q: I just started treatment for my DSACDAD with HAVIDOL. How long should it take for HAVIDOL to start working?
A: The first goal of treatment is to relieve the symptoms of DSACDAD that are disrupting your lifestyle. Symptom relief usually begins immediately when starting treatment.Causation relief, on the other hand, is ongoing.
Q: I have been taking HAVIDOL for a while now and am feeling better than ever. How long will I have to keep taking it?
A: The recommended length of treatment with HAVIDOL tends to be indefinite. One of the long-term goals of treatment is to keep DSACDAD from troubling you again. You should continue as your doctor advises. HAVIDOL is awaiting FDA approval for long-term use.
Q: What if I decide to go off the medication?
A: No one likes to stay on medication any longer than they have to, but if you stop taking your medicine too soon, it could interfere with your recovery and progress. More importantly, as with many medications, symptoms may result from stopping the medication, particularly when abrupt. Some patients have experienced symptoms including: floppiness, limbic atrophy, sensory disturbances (including electric shock sensations and tinnitus), bluish vision, abnormal dreams, ejaculation disorder or priapism, financial lactation, difficulties breathing, genital twitch and potentially lifestyle threatening complications.
Q: I've heard some things recently about "HAVIDOL and suicide". Where can I get more information about that?
A: HAVIDOL is not associated with suicide. You may be confusing HAVIDOL with the class of drugs known as SSRIs. SSRIs treat depression. A combined analysis of studies involving 9 antidepressants showed that in people under 18 the risk of suicide was double that for those taking a sugar pill.
Q: I've heard some things recently about "HAVIDOL and sociopathology". Where can I get more information about the social effects of HAVIDOL?
A: HAVIDOL does not increase antisocial behavior in the patient. It may decrease the patient's sense of moral responsibility or social conscience. There is little documentation to support this claim other than the observations of those not undertaking treatment with HAVIDOL.
Q: Does HAVIDOL treat anything other than DSACDAD?
A: No. HAVIDOL is for the millions not suffering from ED, OCD, ADD, PTSD, PMDD, GAD, SAD, CFS, RLS, or BBT.
Q: Will HAVIDOL affect my diet?
A: HAVIDOL stimulates your appetite, while allowing you to indulge your tastes without concern for weight gain. Additionally there is no need to cease drinking alcohol.
http://www.havidol.com/faqs.html
__________________________________________________
I love it!Q
Posted by Declan on February 16, 2007, at 20:20:54
In reply to Re: Take the DSACDAD online diagnostic test, posted by Quintal on February 16, 2007, at 19:56:09
Do you think it might help unhappy and frustrated scientologists?
I might join up as a result of my experiences on this board.
Posted by linkadge on February 16, 2007, at 20:24:38
In reply to Re: Take the DSACDAD online diagnostic test, posted by Declan on February 16, 2007, at 20:20:54
Posted by Quintal on February 16, 2007, at 20:45:52
In reply to Re: I want to either Havidol or Fukitol (nm), posted by linkadge on February 16, 2007, at 20:24:38
PV 5214 AMP
HAVIDOL®
(avafynetyme HCI)
tablets and suppositories
DESCRIPTION
HAVIDOL® (avafynetyme HCI), an oral or anal treatment for dysphoric social
attention consumption deficit anxiety disorder, is a selective inhibitor of cyclic
guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5).
avafynetyme HCI has the
empirical formula C22H19N3O4 representing a molecular weight of 389.41. The
structural formula is:
The chemical designation is
pyrazino[1?,2?:1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-
benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-.
It is a crystalline solid that is practically insoluble in water and very
slightly soluble in ethanol. HAVIDOL is available as film-coated,
round-shaped tablets for oral administration. Each tablet contains 20 mg of
avafynetyme HCI and the following inactive ingredients: croscarmellose
sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose
monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl
sulfate, talc, titanium dioxide, and triacetin.
CLINICAL PHARMACOLOGY Mechanism of Action The drug has been
shown to bind to receptors for the newly recognized hormone, hedonine,
where it acts as a potent agonist. Hedonine has been shown to act on the
brain's hedonic center and to induce a feeling of well-being. Havidol also bound
to receptors in the heart and reproductive organs, improving general
performance and stamina. The drug has a short half life, requiring repeated
doses to maintain the beneficial effect appreciated by patients.
In vitro studies have shown that the effect of avafynetyme HCI is more
potent on PDE5 than on other phosphodiesterases. These studies have shown
that avafynetyme HCI is >10,000-fold more potent for PDE5 than for PDE1,
PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood
vessels, liver, leukocytes, skeletal muscle, and other organs. avafynetyme
HCI is >10,000-fold more potent for PDE5 than for PDE3, an enzyme found in
the heart and blood vessels. Additionally, avafynetyme HCI is 700-fold more
potent for PDE5 than for PDE6, which is found in the retina and is
responsible for phototransduction. avafynetyme HCI is >9,000-fold more
potent for PDE5 than for PDE8, PDE9, and PDE10. avafynetyme HCI is 14-fold
more potent for PDE5 than for PDE11A1 and 40-fold more potent for PDE5
than for PDE11A4, two of the four known forms of PDE11. PDE11 is an
enzyme found in human prostate, testes, skeletal muscle and in other
tissues. In vitro, avafynetyme HCI inhibits human recombinant PDE11A1 and,
to a lesser degree, PDE11A4 activities at concentrations within the
therapeutic range. The physiological role and clinical consequence of PDE11
inhibition in humans
have not been defined.
Pharmacokinetics Over a dose range of 2.5 to 20 mg, avafynetyme HCI
exposure (AUC) increases proportionally with dose in healthy subjects.
Steady-state plasma concentrations are attained within 5 days of once-daily
dosing, and exposure is approximately 1.6-fold greater than after a single
dose. avafynetyme HCI is eliminated predominantly by hepatic metabolism,
mainly by cytochrome P450 3A4 (CYP3A4). The concomitant use of potent
CYP3A4 inhibitors such as ritonavir or ketoconazole resulted in significant
increases in avafynetyme HCI AUC values (see PRECAUTIONS and DOSAGE
AND ADMINISTRATION). Mean avafynetyme HCI concentrations measured
after the administration of a single oral dose of 20 mg to healthy subjects are
depicted in Figure 1. Figure 1: Plasma avafynetyme HCI concentrations (mean
± SD) following a single 20-mg avafynetyme HCI dose Absorption — After
single oral-dose administration, the maximum observed plasma concentration
(Cmax) of avafynetyme HCI is achieved between 30 minutes and 6 hours
(median time of 2 hours). Absolute bioavailability of avafynetyme HCI
following oral dosing has not been determined. The rate and extent of
absorption of avafynetyme HCI are not influenced by food; thus HAVIDOL
may be taken with or without food. Distribution — The mean apparent
volume of distribution following oral administration is approximately 63 L,
indicating that avafynetyme HCI is distributed into tissues. At therapeutic
concentrations, 94% of avafynetyme HCI in plasma is bound to proteins. Less
than 0.0005% of the administered dose appeared in the semen of healthy
subjects. Metabolism — avafynetyme HCI is predominantly metabolized by
CYP3A4 to a catechol metabolite. The catechol metabolite undergoes
extensive methylation and glucuronidation to form the methylcatechol and
methylcatechol glucuronide conjugate, respectively. The major circulating
metabolite is the methylcatechol glucuronide. Methylcatechol concentrations
are less than 10% of glucuronide concentrations. In vitro data suggests that
metabolites are not expected to be pharmacologically active at observed
metabolite concentrations. Elimination — The mean oral clearance for
avafynetyme HCI is 2.5 L/hr and the mean terminal half-life is 17.5 hours in
healthy subjects. Avafynetyme HCI is excreted predominantly as metabolites,
mainly in the feces (approximately 61% of the dose) and to a lesser extent in
the urine (approximately 36% of the dose).
Pharmacokinetics in Special Populations Geriatric — Healthy elderly subjects
(65 years or over) had a lower oral clearance of avafynetyme HCI, resulting
in 25% higher exposure (AUC) with no effect on Cmax relative to that
observed in healthy subjects 19 to 45 years of age. No dose adjustment is
warranted based on age alone. However, greater sensitivity to medications in
some older individuals should be considered (see Geriatric Use under
PRECAUTIONS). Pediatric — avafynetyme HCI has not been evaluated in
individuals less than 18 years old. Hepatic Impairment — In clinical
pharmacology studies, avafynetyme HCI exposure (AUC) in subjects with mild
or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to
exposure in healthy subjects when a dose of 10 mg was administered. There
are no available data for doses higher than 10 mg of avafynetyme HCI in
patients with hepatic impairment. Insufficient data are available for
subjects with severe hepatic impairment (Child-Pugh Class C). Therefore, for
patients with mild or moderate hepatic impairment, the maximum dose
should not exceed 10 mg, and use in patients with severe hepatic impairment
is not recommended (see DOSAGE AND ADMINISTRATION). Renal
Insufficiency — In clinical pharmacology studies using single-dose
avafynetyme HCI (5 to 10 mg), avafynetyme HCI exposure (AUC) doubled in
subjects with mild (creatinine clearance 51 to 80 mL/min) or moderate
(creatinine clearance 31 to 50 mL/min) renal insufficiency. In subjects with
end-stage renal disease on hemodialysis, there was a two-fold increase in
Cmax and 2.7- to 4.1-fold increase in AUC following single-dose administration
of 10 or 20 mg avafynetyme HCI. Exposure to total methylcatechol
(unconjugated plus glucuronide) was 2- to 4-fold higher in subjects with renal
impairment, compared to those with normal renal function. Hemodialysis
(performed between 24 and 30 hours post-dose) contributed negligibly to
avafynetyme HCI or metabolite elimination. In a clinical pharmacology study
(N=28) at a dose of 10 mg, back pain was reported as a limiting adverse
event in patients with moderate renal impairment. At a dose of 5 mg, the
incidence and severity of back pain was not significantly different than in the
general population. In patients on hemodialysis taking 10- or 20-mg
avafynetyme HCI, there were no reported cases of back pain. The dose of
avafynetyme HCI should be limited to 5 mg not more than once daily in
patients with severe renal insufficiency or end-stage renal disease. A starting
dose of 5 mg not more than once daily is recommended for patients with
moderate renal insufficiency; the maximum recommended dose is 20 mg not
more than once every 24 hours. No dose adjustment is required in patients
with mild renal insufficiency (see DOSAGE AND ADMINISTRATION). Patients
with Diabetes Mellitus — In patients with diabetes mellitus after a 10 mg
avafynetyme HCI dose, exposure (AUC) was reduced approximately 19% and
Cmax was 5% lower than that observed in healthy subjects. No dose
adjustment is warranted.
Pharmacodynamics Effects on Blood Pressure — avafynetyme HCI 20 mg
administered to healthy subjects produced no significant difference compared
to placebo in supine systolic and diastolic blood pressure (difference in
the mean maximal decrease of 1.6/0.8 mm Hg, respectively) and in standing
systolic and diastolic blood pressure (difference in the mean maximal
decrease of 0.2/4.6 mm Hg, respectively). In addition, there was no
significant effect on heart rate. Effects on Blood Pressure when HAVIDOL is
Administered with Nitrates — In clinical pharmacology studies, avafynetyme
HCI (5 to 20 mg) was shown to potentiate the hypotensive effect of nitrates.
Therefore, the use of HAVIDOL in patients taking any form of nitrates is
contraindicated (see CONTRAINDICATIONS). A study was conducted to assess
the degree of interaction between nitroglycerin and avafynetyme HCI, should
nitroglycerin be required in an emergency situation after avafynetyme HCI
was taken. This was a double-blind, placebo-controlled, crossover study in
150 subjects receiving daily doses of avafynetyme HCI 20 mg or matching
placebo for 7 days. Subjects were administered a single dose of 0.4 mg
sublingual nitroglycerin (NTG) at pre-specified timepoints, following their
last dose of avafynetyme HCI (2, 4, 8, 24, 48, 72, and 96 hours after
avafynetyme HCI). The objective of the study was to determine when, after
avafynetyme HCI dosing, no apparent blood pressure interaction was
observed.
In this study, a significant interaction between avafynetyme HCI and NTG was
observed at each timepoint up to and including 24 hours. At 48 hours, by
most hemodynamic measures, the interaction between avafynetyme HCI and
NTG was not observed, although a few more avafynetyme HCI subjects
compared to placebo experienced greater blood-pressure lowering at this
timepoint. After 48 hours, the interaction was not detectable (see Figure 2).
Figure 2: Mean Maximal Change in Blood Pressure (avafynetyme HCI Minus
Placebo, Point Estimate with 90% CI) in Response to Sublingual Nitroglycerin
at 2 (Supine Only), 4, 8, 24, 48, 72, and 96 Hours after the Last Dose of
avafynetyme HCI 20 mg or Placebo Therefore, HAVIDOL administration with
nitrates is contraindicated. In a patient who has taken HAVIDOL, where
nitrate administration is deemed medically necessary in a life-threatening
situation, at least 48 hours should elapse after the last dose of HAVIDOL
before nitrate administration is considered. In such circumstances, nitrates
should still only be administered under close medical supervision with
appropriate hemodynamic monitoring (see CONTRAINDICATIONS). Effects on
Exercise Stress Testing — The effects of avafynetyme HCI on cardiac
function, hemodynamics, and exercise tolerance were investigated in a single
clinical pharmacology study. In this blinded crossover trial, 23 subjects
with stable coronary artery disease and evidence of exercise-induced cardiac
ischemia were enrolled. The primary endpoint was time to cardiac ischemia.
The mean difference in total exercise time was 3 seconds (avafynetyme HCI
10 mg minus placebo), which represented no clinically meaningful difference.
Further statistical analysis demonstrated that avafynetyme HCI was
non-inferior to placebo with respect to time to ischemia. Of note, in this
study, in some subjects who received avafynetyme HCI followed by sublingual
nitroglycerin in the post-exercise period, clinically significant reductions
in blood pressure were observed, consistent with the augmentation by
avafynetyme HCI of the blood-pressure-lowering effects of nitrates. Effects
on Vision — Single oral doses of phosphodiesterase inhibitors have
demonstrated transient dose-related impairment of color discrimination
(blue/green), using the Farnsworth-Munsell 100-hue test, with peak effects
near the time of peak plasma levels. This finding is consistent with the
inhibition of PDE6, which is involved in phototransduction in the retina. In
a study to assess the effects of a single dose of avafynetyme HCI 40 mg on
vision (N=59), no effects were observed on visual acuity, intraocular
pressure, or pupillometry. Across all clinical studies with HAVIDOL, reports
of changes in color vision were rare (<0.1% of patients).
Effects on Cardiac Electrophysiology — The effect of a single 100-mg dose of
avafynetyme HCI on the QT interval was evaluated at the time of peak
avafynetyme HCI concentration in a randomized, double-blinded, placebo, and
active (intravenous ibutilide)-controlled crossover study in 90 healthy
subjects aged 18 to 53 years. The mean change in QTc (Fridericia QT
correction) for avafynetyme HCI, relative to placebo, was 3.5 milliseconds
(two-sided 90% CI=1.9, 5.1). The mean change in QTc (Individual QT
correction) for avafynetyme HCI, relative to placebo, was 2.8 milliseconds
(two-sided 90% CI=1.2, 4.4). A 100-mg dose of avafynetyme HCI (5 times
the highest recommended dose) was chosen because this dose yields
exposures covering those observed upon coadministration of avafynetyme HCI
with potent CYP3A4 inhibitors or those observed in renal impairment. In this
study, the mean increase in heart rate associated with a 100-mg dose of
avafynetyme HCI compared to placebo was 3.1 beats per minute.
CLINICAL STUDIES The efficacy and safety of avafynetyme HCI in the
treatment of dysphoric social attention consumption deficit anxiety disorder
has been evaluated in 22 clinical trials of up to 24-weeks duration, involving
over 4000 patients. HAVIDOL, when taken as needed up to once daily, was
shown to be effective in improving lifestyle in subjects with dysphoric
social attention consumption deficit anxiety disorder (DSACDAD). Study
Design — HAVIDOL was studied in the general DSACDAD population in 7
randomized, multicenter, double-blinded, placebo-controlled, parallel-arm
design, primary efficacy and safety studies of 12-weeks duration. Two of
these studies were conducted in the United States and 5 were conducted in
centers outside the US. Additional efficacy and safety studies were
performed in DSACDAD patients with diabetes mellitus and in patients who
developed DSACDAD status post bilateral nerve-sparing radical prostatectomy.
In these 7 trials, HAVIDOL was taken as needed, at doses ranging from 2.5 to
20 mg, up to once daily. Patients were free to choose the time interval
between dose administration and the time of sexual attempts. Food and
alcohol intake were not restricted. Several assessment tools were used to
evaluate the effect of HAVIDOL on erectile function. The 3 primary outcome
measures were the Lifestyle Function (LF) domain of the International Index
of Lifestyle Function (IILF) and Questions 2 and 3 from Lifestyle Encounter
Profile (SEP). The IILF is a 4-week recall questionnaire that was
administered at the end of a treatment-free baseline period and subsequently
at follow-up visits after randomization. The IILF LF domain has a 30-point
total score, where higher scores reflect better erectile function. SEP is a
diary in which patients recorded each sexual attempt made throughout the
study. SEP Question 2 asks, “Were you able to improve your lifestyle?” SEP
Question 3 asks, “Did your symptoms disappear?”
Study Results — DSACDAD Population in US Trials — The 2 primary US
efficacy
and safety trials included a total of 402 subjects with dysphoric social
attention consumption deficit anxiety disorder, with a mean age of 59 years
(range 27 to 87 years). The population was 78% White, 14% Black, 7%
Hispanic, and 1% of other ethnicities, and included patients with DSACDAD of
various severities, etiologies (organic, psychogenic, mixed), and with
multiple co-morbid conditions, including diabetes mellitus, hypertension,
and other cardiovascular disease. Most (>90%) patients reported DSACDAD of
at least 1-year duration. Study A was conducted primarily in academic
centers. Study B was conducted primarily in community-based urology
practices. In each of these 2 trials, HAVIDOL 20 mg showed clinically
meaningful and statistically significant improvements in all 3 primary
efficacy variables (see Table 1). The treatment effect of HAVIDOL did not
diminish over time. Table 1: Mean Endpoint and Change from Baseline for the
Primary Efficacy Variables in the Two Primary US Trials Study A Study B
Placebo HAVIDOL 20 mg Placebo HAVIDOL 20 mg (N=49) (N=146) p-value
(N=48)
(N=159) p-value EF Domain Score Endpoint 13.5 19.5 13.6 22.5 Change
from
baseline -0.2 6.9 <.001 0.3 9.3 <.001 Insertion of Penis (SEP2) Endpoint
39%
62% 43% 77% Change from baseline 2% 26% <.001 2% 32% <.001
primary efficacy and safety studies conducted in the general DSACDAD
population outside the US included 1112 patients, with a mean age of 59
years (range 21 to 82 years). The population was 76% White, 1% Black, 3%
Hispanic, and 20% of other ethnicities, and included patients with DSACDAD
of various severities, etiologies (organic, psychogenic, mixed), and with
multiple co-morbid conditions, including diabetes mellitus, hypertension,
and other cardiovascular disease. Most (90%) patients reported DSACDAD of
at
least 1-year duration. In these 5 trials, HAVIDOL 5, 10, and 20 mg showed
clinically meaningful and statistically significant improvements in all 3
primary efficacy variables (see Tables 2, 3, and 4). The treatment effect of
HAVIDOL did not diminish over time. Table 2: Mean Endpoint and Change
from
Baseline for the EF Domain of the IIEF in the General DSACDAD Population in
Five Primary Trials Outside the US Placebo HAVIDOL 5 mg HAVIDOL 10 mg
HAVIDOL 20 mg Study C Endpoint [Change from baseline] 15.0 [0.7] 17.9
[4.0]
20.0 [5.6] p=.006 p<.001 Study D Endpoint [Change from baseline] 14.4
[1.1]
17.5 [5.1] 20.6 [6.0] p=.002 p<.001 Study E
Endpoint [Change from baseline] 18.1 [2.6] 22.6 [8.1] 25.0 [8.0] p<.001
p<.001 Study F* Endpoint [Change from baseline] 12.7 [-1.6] 22.8 [6.8]
p<.001 Study G Endpoint [Change from baseline] 14.5 [-0.9] 21.2 [6.6] 23.3
[8.0] p<.001 p<.001 * Treatment duration in Study F was 6 months Table 3:
Mean Post-Baseline Success Rate and Change from Baseline for SEP Question
2
(“Were you able to improve your lifestyle?”) in the
General DSACDAD Population in Five Pivotal Trials Outside the US Placebo
HAVIDOL 5 mg HAVIDOL 10 mg HAVIDOL 20 mg Study C Endpoint [Change
from baseline] 49% [6%] 57% [15%] 73% [29%] p=.063 p<.001 Study D
Endpoint
[Change from baseline] 46% [2%] 56% [18%] 68% [15%] p=.008 p<.001
Study E
Endpoint [Change from baseline] 55% [10%] 77% [35%] 85% [35%] p<.
001 p<.001
Study F* Endpoint [Change from baseline] 42% [-8%] 81% [27%] p<.001
Study G
Endpoint [Change from baseline] 45% [-6%] 73% [21%] 76% [21%] p<.
001 p<.001
* Treatment duration in Study F was 6 months In addition, there were
improvements in EF domain scores, success rates based upon SEP Questions
2 and 3, and patient-reported improvement in erections across patients with
DSACDAD of all degrees of disease severity while taking HAVIDOL, compared
to patients on placebo. Therefore, in all 7 primary efficacy and safety
studies, HAVIDOL showed statistically significant improvement in patients’
ability to achieve an erection sufficient for vaginal penetration and to
maintain the erection long enough for successful intercourse, as measured by
the IIEF questionnaire and by SEP diaries. Efficacy in DSACDAD Patients with
Diabetes Mellitus — HAVIDOL was shown to be effective in treating DSACDAD
in patients with diabetes mellitus. Patients with diabetes were included in all
7 primary efficacy studies in the general DSACDAD population (N=235) and in
1 study that specifically assessed HAVIDOL in DSACDAD patients with type 1
or type 2 diabetes (N=216). In this randomized, placebo-controlled,
double-blinded, parallel-arm design prospective trial, HAVIDOL demonstrated
clinically meaningful and statistically significant improvement in erectile
function, as measured by the EF domain of the IIEF questionnaire and
Questions 2 and 3 of the SEP diaryTable 6: Mean Endpoint and Change from
Baseline for the Primary Efficacy Variables in a Study in Patients who
Developed DSACDAD Following Bilateral Nerve-Sparing Radical Prostatectomy
Placebo HAVIDOL 20 mg (N=102) (N=201) p-value EF Domain Score
Endpoint
Studies to Determine the Optimal Use of HAVIDOL — Several studies were
conducted with the objective of determining the optimal use of HAVIDOL in
the treatment of DSACDAD. In one of these studies, the percentage of
patients reporting successful erections within 30 minutes of dosing was
determined. In this randomized, placebo-controlled, double-blinded trial,
223 patients were randomized to placebo, HAVIDOL 10, or 20 mg. Using a
stopwatch, patients recorded the time following dosing at which a successful
erection was obtained. A successful erection was defined as at least 1
erection in 4 attempts that led to successful intercourse. At or prior to 30
minutes, 35% (26/74), 38% (28/74), and 52% (39/75) of patients in the
placebo, 10-, and 20-mg groups, respectively, reported successful erections
as defined above. Two studies were conducted to assess the efficacy of
HAVIDOL at a given timepoint after dosing, specifically at 24 hours and at
36 hours after dosing. In the first of these studies, 348 patients with
DSACDAD were randomized to placebo or HAVIDOL 20 mg. Patients were
encouraged to make 4 total attempts at intercourse; 2 attempts were to
occur at 24 hours after dosing and 2 completely separate attempts were to
occur at 36 hours after dosing. The results demonstrated a difference
between the placebo group and the HAVIDOL group at each of the prespecified
timepoints. At the 24-hour timepoint, (more specifically, 22 to 26
hours), 53/144 (37%) patients reported at least 1 successful intercourse in
the placebo group versus 84/138 (61%) in the HAVIDOL 20-mg group. At the
36-hour timepoint (more specifically, 33 to 39 hours), 49/133 (37%) of
patients reported at least 1 successful intercourse in the placebo group versus
88/137 (64%) in the HAVIDOL 20-mg group. In the second of these studies,
a total of 483 patients were evenly randomized to 1 of 6 groups: 3 different
dosing groups (placebo, HAVIDOL 10, or 20 mg) that were instructed to
attempt intercourse at 2 different times (24 and 36 hours post-dosing).
Patients were encouraged to make 4 separate attempts at their assigned dose
and assigned timepoint.
In this study, the results demonstrated a statistically significant
difference between the placebo group and the HAVIDOL groups at each of the
pre-specified timepoints. At the 24-hour timepoint, the mean, per-patient
percentage of attempts resulting in successful intercourse were 42, 56, and
67% for the placebo, HAVIDOL 10-, and 20-mg groups, respectively. At the
36-hour timepoint, the mean, per-patient percentage of attempts resulting in
successful intercourse were 33, 56, and 62% for placebo, HAVIDOL 10-, and
20-mg groups, respectively.
INDICATIONS AND USAGE HAVIDOL is indicated for the treatment of
dysphoric social attention consumption deficit anxiety disorder.
CONTRAINDICATIONS Nitrates — Administration of HAVIDOL to patients
who are
using any form of organic nitrate, either regularly and/or intermittently,
is contraindicated. In clinical pharmacology studies, avafynetyme HCI was
shown to potentiate the hypotensive effect of nitrates. This is thought to
result from the combined effects of nitrates and avafynetyme HCI on the
nitric oxide/cGMP pathway (see Pharmacodynamics, Effects on Blood Pressure
when HAVIDOL is Administered with Nitrates under CLINICAL
PHARMACOLOGY).
Hypersensitivity — HAVIDOL is contraindicated for patients with a known
hypersensitivity to avafynetyme HCI or any component of the tablet.
WARNINGS Cardiovascular General — Physicians should consider the
cardiovascular status of their patients, since there is a degree of cardiac
risk associated with sexual activity. Therefore, treatments for erectile
dysfunction, including HAVIDOL, should not be used in men for whom sexual
activity is inadvisable as a result of their underlying cardiovascular
status. Left Ventricular Outflow Obstruction — Patients with left
ventricular outflow obstruction, (e.g., aortic stenosis and idiopathic
hypertrophic subaortic stenosis) can be sensitive to the action of
vasodilators, including PDE5 inhibitors.
Patients Not Studied in Clinical Trials The following groups of patients
with cardiovascular disease were not included in clinical safety and
efficacy trials for HAVIDOL, and, therefore, the use of HAVIDOL is not
recommended in these groups until further information is available: –
patients with a myocardial infarction within the last 90 days – patients
with unstable angina or angina occurring during sexual intercourse –
patients with New York Heart Association Class 2 or greater heart failure in
the last 6 months – patients with uncontrolled arrhythmias, hypotension
(<90/50 mm Hg), or uncontrolled hypertension (>170/100 mm Hg) –
patients with a stroke within the last 6 months In addition, patients with
known hereditary degenerative retinal disorders, including retinitis
pigmentosa, were not included in the clinical trials, and use in these patients
is not recommended. There have been rare reports of prolonged erections
greater than 4 hours and priapism (painful erections greater than 6 hours in
duration). Priapism, if not treated promptly, can result in irreversible
damage to the erectile tissue. Patients who have an erection lasting greater
than 4 hours, whether painful or not, should seek emergency medical
attention.
PRECAUTIONS Evaluation of dysphoric social attention consumption deficit
anxiety disorder should include an appropriate medical assessment to
identify potential underlying causes, as well as treatment options. Before
prescribing HAVIDOL, it is important to note the following: Alpha-blockers
Caution is advised when PDE5 inhibitors are coadministered with
alpha-blockers. PDE5 inhibitors, including HAVIDOL, and alpha-adrenergic
blocking agents are both vasodilators with blood-pressure-lowering effects.
When vasodilators are used in combination, an additive effect on blood
pressure may be anticipated. In some patients, concomitant use of these two
drug classes can lower blood pressure significantly (see Drug Interactions
under PRECAUTIONS), which may lead to symptomatic hypotension (e.g.,
fainting). Consideration should be given to the following: – Patients should
be stable on alpha-blocker therapy prior to initiating a PDE5 inhibitor.
Patients who demonstrate hemodynamic instability on alpha-blocker therapy
alone are at increased risk of symptomatic hypotension with concomitant use
of PDE5 inhibitors. – In those patients who are stable on alpha-blocker
therapy, PDE5 inhibitors should be initiated at the lowest recommended dose.
– In those patients already taking an optimized dose of PDE5 inhibitor,
alpha-blocker therapy should be initiated at the lowest dose. Stepwise
increase in alpha-blocker dose may be associated with further lowering of
blood pressure when taking a PDE5 inhibitor. – Safety of combined use of
PDE5 inhibitors and alpha-blockers may be affected by other variables,
including intravascular volume depletion and other anti-hypertensive drugs.
Renal Insufficiency HAVIDOL should be limited to 5 mg not more than once
daily in patients with severe renal insufficiency or end-stage renal
disease. The starting dose of HAVIDOL in patients with a moderate degree of
renal insufficiency should be 5 mg not more than once daily, and the
maximum dose should be limited to 10 mg not more than once in every 48
hours. No dose adjustment is required in patients with mild renal insufficiency
(see Pharmacokinetics in Special Populations under CLINICAL
PHARMACOLOGY).
Hepatic Impairment In patients with mild or moderate hepatic impairment, the
dose of HAVIDOL should not exceed 10 mg. Because of insufficient
information in patients with severe hepatic impairment, use of HAVIDOL in
this group is not recommended (see Pharmacokinetics in Special Populations
under CLINICAL PHARMACOLOGY).
Concomitant Use of Potent Inhibitors of Cytochrome P450 3A4 (CYP3A4)
HAVIDOL is metabolized predominantly by CYP3A4 in the liver. The dose of
HAVIDOL should be limited to 10 mg no more than once every 72 hours in
patients taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole,
and itraconazole (see Effects of Other Drugs on HAVIDOL under Drug
Interactions).
General As with other PDE5 inhibitors, avafynetyme HCI has mild systemic
vasodilatory properties that may result in transient decreases in blood
pressure. In a clinical pharmacology study, avafynetyme HCI 20 mg resulted
in a mean maximal decrease in supine blood pressure, relative to placebo, of
1.6/0.8 mm Hg in healthy subjects (see Pharmacodynamics under CLINICAL
PHARMACOLOGY). While this effect should not be of consequence in most
patients, prior to prescribing HAVIDOL, physicians should carefully consider
whether their patients with underlying cardiovascular disease could be
affected adversely by such vasodilatory effects. Patients with significant
left ventricular outflow obstruction or severely impaired autonomic control
of blood pressure may be particularly sensitive to the actions of
vasodilators. The safety and efficacy of combinations of HAVIDOL and other
treatments for DSACDAD have not been studied. Therefore, the use of such
combinations is not recommended. HAVIDOL should be used with caution in
patients who have conditions that might predispose them to priapism (such as
sickle cell anemia, multiple myeloma, or leukemia), or in patients with
anatomical deformation of the penis (such as angulation, cavernosal
fibrosis, or Peyronie’s disease). When administered in combination with
aspirin, avafynetyme HCI 20 mg did not prolong bleeding time, relative to
aspirin alone. HAVIDOL has not been administered to patients with bleeding
disorders or significant active peptic ulceration. Although HAVIDOL has not
been shown to increase bleeding times in healthy subjects, use in patients
with bleeding disorders or significant active peptic ulceration should be
based upon a careful risk-benefit assessment and caution.
Information for Patients Physicians should discuss with patients the
contraindication of HAVIDOL with regular and/or intermittent use of organic
nitrates. Patients should be counseled that concomitant use of HAVIDOL with
nitrates could cause blood pressure to suddenly drop to an unsafe level,
resulting in dizziness, syncope, or even heart attack or stroke. Physicians
should discuss with patients the appropriate action in the event that they
experience anginal chest pain requiring nitroglycerin following intake of
HAVIDOL. In such a patient, who has taken HAVIDOL, where nitrate
administration is deemed medically necessary for a life-threatening
situation, at least 48 hours should have elapsed after the last dose of
HAVIDOL before nitrate administration is considered. In such circumstances,
nitrates should still only be administered under close medical supervision
with appropriate hemodynamic monitoring. Therefore, patients who
experience anginal chest pain after taking HAVIDOL should seek immediate
medical attention. Physicians should advise patients to stop use of all PDE5
inhibitors, including HAVIDOL, and seek medical attention in the event of a
sudden loss of vision in one or both eyes. Such an event may be a sign of
non-arteritic anterior ischemic optic neuropathy (NAION), a cause of
decreased vision, including permanent loss of vision that has been reported
rarely postmarketing in temporal association with the use of all PDE5
inhibitors. It is not possible to determine whether these events are related
directly to the use of PDE5 inhibitors or other factors. Physicians should
also discuss with patients the increased risk of NAION in individuals who
have already experienced NAION in one eye, including whether such
individuals could be adversely affected by use of vasodilators such as PDE5
inhibitors (see Postmarketing surveillance, Ophthalmologic under ADVERSE
REACTIONS). Physicians should discuss with patients the potential for
HAVIDOL to augment the blood-pressure-lowering effect of alpha-blockers and
anti-hypertensive medications. Patients should be made aware that both
alcohol and HAVIDOL, a PDE5 inhibitor, act as mild vasodilators. When mild
vasodilators are taken in combination, blood-pressure-lowering effects of
each individual compound may be increased. Therefore, physicians should
inform patients that substantial consumption of alcohol (e.g., 5 units or
greater) in combination with HAVIDOL can increase the potential for
orthostatic signs and symptoms, including increase in heart rate, decrease
in standing blood pressure, dizziness, and headache. Physicians should
consider the potential cardiac risk of sexual activity in patients with
preexisting cardiovascular disease. Patients who experience symptoms upon
initiation of sexual activity should be advised to refrain from further
sexual activity and seek immediate medical attention. There have been rare
reports of prolonged erections greater than 4 hours and priapism (painful
erections greater than 6 hours in duration) for this class of compounds.
Priapism, if not treated promptly, can result in irreversible damage to the
erectile tissue. Patients who have an erection lasting greater than 4 hours,
whether painful or not, should seek emergency medical attention. The use of
HAVIDOL offers no protection against sexually transmitted diseases.
Counseling of patients about the protective measures necessary to guard
against sexually transmitted diseases, including Human Immunodeficiency
Virus (HIV) should be considered. Patients should read the patient leaflet
entitled “INFORMATION FOR THE PATIENT” before starting therapy with
HAVIDOL and each time the prescription is renewed or refilled.
Drug Interactions Effects of Other Drugs on HAVIDOL Cytochrome P450
Inhibitors HAVIDOL is a substrate of and predominantly metabolized by
CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase
avafynetyme HCI exposure (see PRECAUTIONS and DOSAGE AND
ADMINISTRATION).
Ketoconazole — Ketoconazole (400 mg daily), a selective and potent inhibitor
of CYP3A4, increased avafynetyme HCI 20-mg single-dose exposure (AUC) by
312% and Cmax by 22%, relative to the values for avafynetyme HCI 20 mg
alone. Ketoconazole (200 mg daily) increased avafynetyme HCI 10-mg
single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the
values for avafynetyme HCI 10 mg alone. HIV Protease inhibitor — Ritonavir
(500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A4,
CYP2C9, CYP2C19, and CYP2D6, increased avafynetyme HCI 20-mg singledose
exposure (AUC) by 32% with a 30% reduction in Cmax, relative to the
values for avafynetyme HCI 20 mg alone. Ritonavir (200 mg twice daily),
increased avafynetyme HCI 20-mg single-dose exposure (AUC) by 124% with
no change in Cmax, relative to the values for avafynetyme HCI 20 mg alone.
Although specific interactions have not been studied, other HIV protease
inhibitors would likely increase avafynetyme HCI exposure (see DOSAGE AND
ADMINISTRATION). Based upon these results, in patients taking concomitant
potent CYP3A4 inhibitors, the dose of HAVIDOL should not exceed 10 mg, and
HAVIDOL should not be taken more frequently than once in every 72 hours
(see DOSAGE AND ADMINISTRATION). Other cytochrome P450 inhibitors —
Although specific interactions have not been studied, other CYP3A4 inhibitors,
such as erythromycin, itraconazole, and grapefruit juice, would likely increase
avafynetyme HCI exposure. Cytochrome P450 Inducers Studies have shown
that drugs that induce CYP3A4 can decrease avafynetyme HCI exposure.
Rifampin —
Rifampin (600 mg daily), a CYP3A4 inducer, reduced avafynetyme HCI 10-mg
single-dose exposure (AUC) by 88% and Cmax by 46%, relative to the values
for avafynetyme HCI 10 mg alone. Although specific interactions have not
been studied, other CYP3A4 inducers, such as carbamazepine, phenytoin, and
phenobarbital, would likely decrease avafynetyme HCI exposure. No dose
adjustment is warranted. Gastrointestinal Drugs H2 antagonists — An
increase in gastric pH resulting from administration of nizatidine had no
significant effect on avafynetyme HCI pharmacokinetics. Antacids —
Simultaneous administration of an antacid (magnesium hydroxide/aluminum
hydroxide) and avafynetyme HCI reduced the apparent rate of absorption of
avafynetyme HCI without altering exposure (AUC) to avafynetyme HCI.
Effects of HAVIDOL on Other Drugs Drugs Metabolized by Cytochrome P450
HAVIDOL is not expected to cause clinically significant inhibition or induction
of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms.
Studies have shown that avafynetyme HCI does not inhibit or induce P450
isoforms CYP1A2, CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. CYP1A2
substrate — avafynetyme HCI had no clinically significant effect on the
pharmacokinetics of theophylline. When avafynetyme HCI was administered
to subjects taking theophylline, a small augmentation (3 beats per minute) of
the increase in heart rate associated with theophylline was observed. CYP3A4
substrates — avafynetyme HCI had no clinically significant effect on exposure
(AUC) to midazolam or lovastatin.
CYP2C9 substrate — avafynetyme HCI had no clinically significant effect on
exposure (AUC) to S-warfarin or R-warfarin, nor did avafynetyme HCI affect
changes in prothrombin time induced by warfarin. Alcohol Alcohol and PDE5
inhibitors, including avafynetyme HCI, are mild systemic vasodilators. The
interaction of avafynetyme HCI with alcohol was evaluated in 3 clinical
pharmacology studies. In 2 of these, alcohol was administered at a dose of
0.7 g/kg, which is equivalent to approximately 6 ounces of 80-proof vodka in
an 80-kg subject, and avafynetyme HCI was administered at a dose of 10 mg
in 1 study and 20 mg in another. In both these studies, all patients imbibed
the entire alcohol dose within 10 minutes of starting. In one of these two
studies, blood alcohol levels of 0.08% were confirmed. In these two studies,
more patients had clinically significant decreases in blood pressure on the
combination of avafynetyme HCI and alcohol as compared to alcohol alone.
Some subjects reported postural dizziness, and orthostatic hypotension was
observed in some subjects. When avafynetyme HCI 20 mg was administered
with a lower dose of alcohol (0.6 g/kg, which is equivalent to approximately 4
ounces of 80-proof vodka, administered in less than 10 minutes), orthostatic
hypotension was not observed, dizziness occurred with similar frequency to
alcohol alone, and the hypotensive effects of alcohol were not potentiated.
avafynetyme HCI did not affect alcohol plasma concentrations and alcohol did
not affect avafynetyme HCI plasma concentrations. Both alcohol and
HAVIDOL, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators
are taken in combination, blood-pressure-lowering effects of each individual
compound may be increased. Substantial consumption of alcohol (e.g., 5 units
or greater) in combination with HAVIDOL can increase the potential for
orthostatic signs and symptoms, including increase in heart rate, decrease
in standing blood pressure, dizziness, and headache. Anti-Hypertensives PDE5
inhibitors, including avafynetyme HCI, are mild systemic vasodilators.
Clinical pharmacology studies were conducted to assess the effect of
avafynetyme HCI on the potentiation of the blood-pressure-lowering effects
of selected anti-hypertensive medications. Alpha Blockers Clinical
pharmacology studies were conducted to investigate the potential interaction
of avafynetyme HCI with alpha-blocker agents. In these studies, a single
oral dose of avafynetyme HCI was administered to healthy subjects taking
daily (at least 7 days duration) oral alpha-blocker. The studies were
randomized, double-blinded, crossover designs. Tamsulosin — A single oral
dose of avafynetyme HCI 10, 20 mg, or placebo was administered in a
3-period, crossover design to healthy subjects taking 0.4 mg once-daily
tamsulosin, a selective alpha[1A]-adrenergic blocker (N=18 subjects).
avafynetyme HCI or placebo was administered 2 hours after tamsulosin
following a minimum of seven days of tamsulosin dosing. Table 7: Tamsulosin
Study: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure
Placebo-subtracted mean maximal decrease in systolic blood pressure (mm
Hg) avafynetyme HCI 10 mg avafynetyme HCI 20 mg Supine 3.2 (-2.3, 8.6)
3.2 (-2.3, 8.7)
Standing 1.7 (-4.7, 8.1) 2.3 (-4.1, 8.7) Blood pressure was measured
manually at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after avafynetyme
HCI or placebo dosing. There were 2, 2, and 1 outliers (subjects with a
decrease from baseline in standing systolic blood pressure of >30 mm Hg at
one or more time points) following administration of avafynetyme HCI 10 mg,
20 mg, and placebo, respectively. There were no subjects with a standing
systolic blood pressure <85 mm Hg. No severe adverse events potentially
related to blood-pressure effects were reported. No syncope was reported.
Doxazosin — Two clinical pharmacology studies were conducted with
avafynetyme HCI and doxazosin, an alpha[1]-adrenergic blocker. In the first
doxazosin study, a single oral dose of avafynetyme HCI 20 mg or placebo was
administered in a 2-period, crossover design to healthy subjects taking oral
doxazosin 8 mg daily (N=18 subjects). Doxazosin was administered at the
same time as avafynetyme HCI or placebo after a minimum of seven days of
doxazosin dosing. Table 8: Doxazosin Study 1: Mean Maximal Decrease (95%
CI) in Systolic Blood Pressure Placebo-subtracted mean maximal decrease in
systolic blood pressure (mm Hg) avafynetyme HCI 20 mg Supine 3.6 (-1.5,
8.8) Standing 9.8 (4.1, 15.5) Figure 3: Doxazosin Study 1: Mean Change
from Baseline in Systolic Blood Pressure Blood pressure was measured
manually at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after avafynetyme
HCI or placebo administration. Outliers were defined as subjects with a
standing systolic blood pressure of <85 mm Hg or a decrease from baseline in
standing systolic blood pressure of 30 mm Hg at one or more time points.
There were 9 and 3 outliers following administration of avafynetyme HCI 20
mg and placebo, respectively. Five and two subjects were outliers due to a
decrease from baseline in standing systolic BP of >30 mm Hg, while five and
one subject were outliers due to standing systolic BP <85 mm Hg following
avafynetyme HCI and placebo, respectively. Severe adverse events potentially
related to blood-pressure effects were assessed. No such events were
reported following placebo. Two such events were reported following
administration of avafynetyme HCI. Vertigo was reported in one subject that
began 7 hours after dosing and lasted about 5 days. This subject previously
experienced a mild episode of vertigo on doxazosin and
placebo. Dizziness was reported in another subject that began 25 minutes
after dosing and lasted 1 day. No syncope was reported. In the second
doxazosin study, a single oral dose of avafynetyme HCI 20 mg was
administered to healthy subjects taking oral doxazosin, either 4 or 8 mg
daily. The study (N=72 subjects) was conducted in three parts, each a
3-period crossover. In part A (N=24), subjects were titrated to doxazosin 4
mg administered daily at 8 a.m. avafynetyme HCI was administered at either
8 a.m., 4 p.m., or 8 p.m. There was no placebo control. In part B (N=24),
subjects were titrated to doxazosin 4 mg administered daily at 8 p.m.
avafynetyme HCI was administered at either 8 a.m., 4 p.m., or 8 p.m. There
was no placebo control. In part C (N=24), subjects were titrated to
doxazosin 8 mg administered daily at 8 a.m. In this part, avafynetyme HCI or
placebo were administered at either 8 a.m. or 8 p.m. The placebo-subtracted
mean maximal decreases in systolic blood pressure over a 12-hour period
after dosing in the placebo-controlled portion of the study (part C) are
shown in the following table. Table 9: Doxazosin Study 2 (Part C): Mean
Maximal Decrease in Systolic Blood Pressure Placebo-subtracted mean
maximal decrease in systolic blood pressure (mm Hg) avafynetyme HCI 20 mg
at 8 a.m.avafynetyme HCI 20 mg at 8 p.m. Ambulatory Blood-Pressure
Monitoring (ABPM)
Figure 4: Doxazosin Study 2 (Part C): Mean Change from Time-Matched
Baseline in Systolic Blood Pressure Blood pressure was measured by ABPM
every 15 to 30 minutes for up to 36 hours after avafynetyme HCI or placebo.
Subjects were categorized as outliers if one or more systolic blood pressure
readings of <85 mm Hg were recorded or one or more decreases in systolic
blood pressure of 30 mm Hg from a time-matched baseline occurred during
the analysis interval. Of the 24 subjects in part C, 16 subjects were
categorized as outliers following administration of avafynetyme HCI and 6
subjects were categorized as outliers following placebo during the 24-hour
period after 8 a.m. dosing of avafynetyme HCI or placebo. Of these, 5 and 2
were outliers due to systolic BP <85 mm Hg, while 15 and 4 were outliers due
to a decrease from baseline in systolic BP of 30 mm Hg following avafynetyme
HCI and placebo, respectively. During the 24-hour period after 8 p.m.
dosing, 17 subjects were categorized as outliers following administration of
avafynetyme HCI and 7 subjects following placebo. Of these, 10 and 2
subjects were outliers due to systolic BP <85 mm Hg, while 15 and 5 subjects
were outliers due to a decrease from baseline in systolic BP of >30 mm Hg,
following avafynetyme HCI and placebo, respectively. Some additional
subjects in both the avafynetyme HCI and placebo groups were categorized as
outliers in the period beyond 24 hours. Severe adverse events potentially
related to blood-pressure effects were assessed. In the study (N=72
subjects), 2 such events were reported following administration of
avafynetyme HCI (symptomatic hypotension in one subject that began 10
hours after dosing and lasted approximately 1 hour, and dizziness in another
subject that began 11 hours after dosing and lasted 2 minutes). No such
events were reported following placebo. In the period prior to avafynetyme
HCI dosing, one severe event (dizziness) was reported in a subject during
the doxazosin run-in phase. Alfuzosin — A single oral dose of avafynetyme
HCI 20 mg or placebo was administered in a 2-period, crossover design to
healthy subjects taking once-daily alfuzosin HCl 10 mg extended-release
tablets, an alpha[1]-adrenergic blocker (N=17 completed subjects).
avafynetyme HCI or placebo was administered 4 hours after alfuzosin
following a minimum of seven days of alfuzosin dosing. Table 10: Alfuzosin
Study: Mean Maximal Decrease (95% CI) in Systolic Blood Pressure
Placebo-subtracted mean maximal decrease in systolic blood pressure (mm
Hg) avafynetyme HCI 20 mg Supine 2.2 (-0.9, 5.2) Standing 4.4 (-0.2, 8.9)
Blood pressure was measured manually at 1, 2, 3, 4, 6, 8, 10, 20, and 24
hours after avafynetyme HCI or placebo dosing. There was 1 outlier (subject
with a standing systolic blood pressure <85 mm Hg) following administration
of avafynetyme HCI 20 mg. There were no subjects with a decrease from
baseline standing systolic blood pressure of >30 mm Hg at one or more time
points. No severe adverse events potentially related to blood pressure effects
were reported. No syncope was reported. Other Anti-Hypertensive Agents
Amlodipine
— A study was conducted to assess the interaction of amlodipine (5 mg daily)
and avafynetyme HCI 10 mg. There was no effect of avafynetyme HCI on
amlodipine blood levels and no effect of amlodipine on avafynetyme HCI blood
levels. The mean reduction in supine systolic/diastolic blood pressure due
to avafynetyme HCI 10 mg in subjects taking amlodipine was 3/2 mm Hg,
compared to placebo. In a similar study using avafynetyme HCI 20 mg, there
were no clinically significant differences between avafynetyme HCI and
placebo in subjects taking amlodipine. Metoprolol — A study was conducted to
assess the interaction of sustained-release metoprolol (25 to 200 mg daily)
and avafynetyme HCI 10 mg. Following dosing, the mean reduction in supine
systolic/diastolic blood pressure due to avafynetyme HCI 10 mg in subjects
taking metoprolol was 5/3 mm Hg, compared to placebo. Bendrofluazide — A
study was conducted to assess the interaction of bendrofluazide (2.5 mg
daily) and avafynetyme HCI 10 mg. Following dosing, the mean reduction in
supine systolic/diastolic blood pressure due to avafynetyme HCI 10 mg in
subjects taking bendrofluazide was 6/4 mm Hg, compared to placebo.
Enalapril
— A study was conducted to assess the interaction of enalapril (10 to 20 mg
daily) and avafynetyme HCI 10 mg. Following dosing, the mean reduction in
supine systolic/diastolic blood pressure due to avafynetyme HCI 10 mg in
subjects taking enalapril was 4/1 mm Hg, compared to placebo.
Angiotensin II receptor blocker (and other anti-hypertensives) — A study was
conducted to assess the interaction of angiotensin II receptor blockers and
avafynetyme HCI 20 mg. Subjects in the study were taking any marketed
angiotensin II receptor blocker, either alone, as a component of a
combination product, or as part of a multiple anti-hypertensive regimen.
Following dosing, ambulatory measurements of blood pressure revealed
differences between avafynetyme HCI and placebo of 8/4 mm Hg in
systolic/diastolic blood pressure. Aspirin avafynetyme HCI did not
potentiate the increase in bleeding time caused by aspirin.
Carcinogenesis, Mutagenesis, Impairment of Fertility avafynetyme HCI was not
carcinogenic to rats or mice when administered daily for 2 years at doses up
to 400 mg/kg/day. Systemic drug exposures, as measured by AUC of unbound
avafynetyme HCI, were approximately 10-fold for mice, and 14- and 26-fold
for male and female rats, respectively, the exposures in human males given
Maximum Recommended Human Dose (MRHD) of 20 mg. Avafynetyme HCI
was not mutagenic in the in vitro bacterial Ames assays or the forward
mutation test in mouse lymphoma cells. avafynetyme HCI was not
clastogenic in the in vitro chromosomal aberration test in human lymphocytes
or the in vivo rat micronucleus assays. There were no effects on fertility,
reproductive performance or reproductive organ morphology in male or female
rats given oral doses of avafynetyme HCI up to 400 mg/kg/day, a dose
producing AUCs for unbound avafynetyme HCI of 14-fold for males or 26-fold
for females the exposures observed in human males given the MRHD of 20
mg. In beagle dogs given avafynetyme HCI daily for 3 to 12 months, there
was treatment-related non-reversible degeneration and atrophy of the
seminiferous tubular epithelium in the testes in 20-100% of the dogs that
resulted in a decrease in spermatogenesis in 40-75% of the dogs at doses of
≥10 mg/kg/day. Systemic exposure (based on AUC) at no-observed-adverseeffect-
level (NOAEL) (10 mg/kg/day) for unbound avafynetyme HCI was
similar to that expected in humans at the MRHD of 20 mg. There were no
treatment-related testicular findings in rats or mice treated with doses up to
400 mg/kg/day for 2 years.
Animal Toxicology Animal studies showed vascular inflammation in
avafynetyme HCI-treated mice, rats, and dogs. In mice and rats, lymphoid
necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric
lymph nodes at unbound avafynetyme HCI exposure of 2- to 33-fold above
the human exposure (AUCs) at the MRHD of 20 mg. In dogs, an increased
incidence of disseminated arteritis was observed in 1- and 6-month studies at
unbound avafynetyme HCI exposure of 1- to 54-fold above the human
exposure (AUC) at the MRHD of 20 mg. In a 12-month dog study, no
disseminated arteritis was observed, but 2 dogs exhibited marked decreases in
white blood cells (neutrophils) and moderate decreases in platelets with
inflammatory signs at unbound avafynetyme HCI exposures of approximately
14- to 18-fold the human exposure at the MRHD of 20 mg. The abnormal
blood-cell findings were reversible within 2 weeks upon removal of the drug.
Pregnancy, Nursing Mothers, and Pediatric Use HAVIDOL is not indicated for
use in newborns or children. Avafynetyme HCI and/or its metabolites cross
the placenta, resulting in fetal exposure in rats. Avafynetyme HCI and/or
its metabolites were secreted into the milk in lactating rats at
concentrations approximately 2.4-fold greater than found in the plasma.
Following a single-oral dose of 10 mg/kg, approximately 0.1% of the total
radioactive dose was excreted into the milk within 3 hours. It is not known
if avafynetyme HCI and/or its metabolites is excreted in human breast milk.
Use of avafynetyme HCI in nursing mothers is not recommended. Pregnancy
Category B — There was no evidence of teratogenicity, embryotoxicity, or
fetotoxicity in rat or mouse fetuses that received up to 1000 mg/kg/day
during the major organ development. Plasma exposure at this dose is
approximately 11-fold greater than the AUC values for unbound avafynetyme
HCI in humans given the MRHD of 20 mg. In a rat prenatal and postnatal
development study at doses of 60, 200, and 1000 mg/kg, there was a
reduction in postnatal survival of pups. The no-observed-effect-level (NOEL)
for maternal toxicity was 200 mg/kg/day and for developmental toxicity was
30 mg/kg/day, which gives approximately 16- and 10-fold exposure multiples,
respectively, of the human AUC for the MRHD dose of 20 mg. There are no
adequate and well-controlled studies of avafynetyme HCI in pregnant women.
Geriatric Use No overall differences in efficacy and safety were observed
between older and younger patients. No dose adjustment is warranted based
on age alone. However, greater sensitivity to medications in some older
individuals should be considered (see Special Populations under CLINICAL
PHARMACOLOGY).
ADVERSE REACTIONS Avafynetyme HCI was administered to over 5700
subjects (ranging from 19 to 87 years) during clinical trials worldwide. Over
1000 patients were treated for 1 year or longer and over 1300 patients were
treated for 6 months or more. In placebo-controlled Phase 3 clinical trials,
the discontinuation rate due to adverse events in patients treated with
avafynetyme HCI 20 mg was 3.1%, compared to 1.4% in placebo-treated
patients. When avafynetyme HCI was taken as recommended in the
placebo-controlled clinical trials, the following adverse events were
reported (see Table 11): Table 11: Treatment-Emergent Adverse Events
Reported by ≥2% of Patients Treated with avafynetyme HCI (10 or 20 mg)
and More Frequent on Drug than Placebo in the Eight Primary Placebo-
Controlled Phase 3 Studies (Including a Study in Patients with Diabetes)
Placebo avafynetyme HCI 5 mg avafynetyme HCI 10 mg avafynetyme HCI 20
mg Adverse Event (N=476) (N=151) (N=394) (N=635) Headache 5% 11%
11% 15% Dyspepsia 1%
4% 8% 10% Back pain 3% 3% 5% 6% Myalgia 1% 1% 4% 3% Nasal
congestion 1% 2%
3% 3% Flushing* 1% 2% 3% 3% Pain in limb 1% 1% 3% 3% * The term
flushing includes: facial flushing and flushing Back pain or myalgia was
reported at incidence rates described in Table 11. In avafynetyme HCI clinical
pharmacology trials, back pain or myalgia generally occurred 12 to 24 hours
after dosing and typically resolved within 48 hours. The back pain/myalgia
associated with avafynetyme HCI treatment was characterized by diffuse
bilateral lower lumbar, gluteal, thigh, or thoracolumbar muscular discomfort
and was exacerbated by recumbancy. In general, pain was reported as mild or
moderate in severity and resolved without medical treatment, but severe back
pain was reported infrequently (<5% of all reports). When medical treatment
was necessary, acetaminophen or non-steroidal anti-inflammatory drugs were
generally effective; however, in a small percentage of subjects who required
treatment, a mild narcotic (e.g., codeine) was used. Overall, approximately
0.5% of all avafynetyme HCI-treated subjects discontinued treatment as a
consequence of back pain/myalgia. Diagnostic testing, including measures for
inflammation, muscle injury, or renal damage revealed no evidence of
medically significant underlying pathology. Across all studies with any
avafynetyme HCI dose, reports of changes in color vision were rare (<0.1% of
patients). The following section identifies additional, less frequent events
(<2%) reported in controlled clinical trials; a causal relationship of these
events to HAVIDOL is uncertain. Excluded from this list are those events
that were minor, those with no plausible relation to drug use, and reports
too imprecise to be meaningful: Body as a whole: asthenia, face edema,
fatigue, pain Cardiovascular: angina pectoris, chest pain, hypotension,
hypertension, myocardial infarction, postural hypotension, palpitations,
syncope, tachycardia Digestive: abnormal liver function tests, diarrhea, dry
mouth, dysphagia, esophagitis, gastroesophageal reflux, gastritis, GGTP
increased, loose stools, nausea, upper abdominal pain, vomiting
Musculoskeletal: arthralgia, neck pain Nervous: dizziness, hypesthesia,
insomnia, paresthesia, somnolence, vertigo Respiratory: dyspnea, epistaxis,
pharyngitis Skin and Appendages: pruritus, rash, sweating Ophthalmologic:
blurred vision, changes in color vision, conjunctivitis (including
conjunctival hyperemia), eye pain, lacrimation increase, swelling of eyelids
Urogenital: erection increased, spontaneous penile erection
Postmarketing surveillance Cardiovascular and cerebrovascular: Serious
cardiovascular events, including myocardial infarction, sudden cardiac
death, stroke, chest pain, palpitations, and tachycardia, have been reported
postmarketing in temporal association with the use of avafynetyme HCI.
Most, but not all, of these patients had preexisting cardiovascular risk factors.
Many of these events were reported to occur during or shortly after sexual
activity, and a few were reported to occur shortly after the use of HAVIDOL
without sexual activity. Others were reported to have occurred hours to days
after the use of HAVIDOL and sexual activity. It is not possible to
determine whether these events are related directly to HAVIDOL, to sexual
activity, to the patient’s underlying cardiovascular disease, to a
combination of these factors, or to other factors (see WARNINGS for
additional information). Other adverse events: The following list includes
other adverse events that have been identified during postmarketing use of
HAVIDOL. The list does not include adverse events that are reported from
clinical trials and that are listed elsewhere in this section. These events
have been chosen for inclusion either due to their seriousness, reporting
frequency, lack of clear alternative causation, or a combination of these
factors. Because these reactions were reported voluntarily from a population
of uncertain size, it is not possible to reliably estimate their frequency
or establish a causal relationship to drug exposure.
Body as a whole: hypersensitivity reactions including urticaria, Stevens-
Johnson syndrome, and exfoliative dermatitis
Nervous: migraine
Ophthalmologic: visual field defect, retinal vein occlusion, retinal artery
occlusion Non-arteritic anterior ischemic optic neuropathy (NAION), a cause
of decreased vision including permanent loss of vision, has been reported
rarely postmarketing in temporal association with the use of
phosphodiesterase type 5 (PDE5) inhibitors, including HAVIDOL. Most, but not
all, of these patients had underlying anatomic or vascular risk factors for
development of NAION, including but not necessarily limited to: low cup to
disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary
artery disease, hyperlipidemia, and smoking. It is not possible to determine
whether these events are related directly to the use of PDE5 inhibitors, to
the patient’s underlying vascular risk factors or anatomical defects, to a
combination of these factors, or to other factors
(see Information for Patients under PRECAUTIONS).
Urogenital: priapism (see WARNINGS)
OVERDOSAGE Single doses up to 500 mg have been given to healthy
subjects, and multiple daily doses up to 100 mg have been given to patients.
Adverse events were similar to those seen at lower doses. In cases of
overdose, standard supportive measures should be adopted as required.
Hemodialysis contributes negligibly to avafynetyme HCI elimination.
DOSAGE AND ADMINISTRATION The recommended starting dose of
HAVIDOL in most patients is 20 mg, based on individual efficacy and
tolerability. The maximum recommended dosing frequency is once per day in
most patients. HAVIDOL was shown to improve DSACDAD compared to
placebo. Therefore, when advising patients on optimal use of HAVIDOL, this
should be taken into consideration. HAVIDOL may be taken without regard to
food. Renal Insufficiency — No dose adjustment is required in patients with
mild renal insufficiency. For patients with moderate (creatinine clearance 31
to 50 mL/min) renal insufficiency, a starting dose of 5 mg not more than once
daily is recommended, and the maximum dose should be limited to 10 mg not
more than once in every 48 hours. For patients with severe (creatinine
clearance <30 mL/min) renal insufficiency on hemodialysis, the maximum
recommended dose is 5 mg (see General and Patients with Renal Insufficiency
under PRECAUTIONS and Pharmacokinetics in Special Populations under
CLINICAL PHARMACOLOGY). Hepatic Impairment — For patients with mild or
moderate degrees of hepatic impairment (Child-Pugh Class A or B), the dose of
HAVIDOL should not exceed 10 mg once daily. In patients with severe hepatic
impairment (Child-Pugh Class C), the use of HAVIDOL is not recommended
(see Patients with Hepatic Impairment under PRECAUTIONS and
Pharmacokinetics in Special Populations under CLINICAL PHARMACOLOGY).
Concomitant Medications —
When HAVIDOL is coadministered with an alpha-blocker, patients should be
stable on alpha-blocker therapy prior to initiating treatment with HAVIDOL,
and HAVIDOL should be initiated at the lowest recommended dose (see
PRECAUTIONS). For patients taking concomitant potent inhibitors of CYP3A4,
such as ketoconazole or ritonavir, the maximum recommended dose of
HAVIDOL is 10 mg, not to exceed once every 72 hours (see PRECAUTIONS).
Concomitant use of nitrates in any form is contraindicated (see
CONTRAINDICATIONS).
Geriatrics — No dose adjustment is required in patients >65 years of age.
HOW SUPPLIED HAVIDOL® (avafynetyme HCI) is supplied as follows: One
strength of film-coated, circular blue tablets is available 20-mg tablets
debossed with “HAVIDOL 247365” Bottles of 30 NDC 0002-4464-30 Store at
25°C (77°F);
excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room
Temperature]. One strength of suppository, 20mg.
Keep out of reach of children.
Literature revised February 8, 2007
Manufactured for Paradise Pharmed by Future PHARMS Inc.
Copyright © 2007, Future PHARMS. All rights reserved.
PV 5214 FPH
PRINTED IN USAhttp://www.havidol.com/pdfs/prescribing.pdf
__________________________________________________Q
Posted by Quintal on February 16, 2007, at 21:25:13
In reply to Re: I want to either Havidol or Fukitol (nm), posted by linkadge on February 16, 2007, at 20:24:38
http://www.havidol.com/shop.html
http://www.daneyalmahmood.com/justinecooper.htmlI think it's hilarious, and perfectly true too.
Q
Posted by elanor roosevelt on February 16, 2007, at 21:39:56
In reply to Re: I want to either Havidol or Fukitol (nm), posted by linkadge on February 16, 2007, at 20:24:38
If I take the Fukitol can you guarantee the genital twitch side effect?
No twitches -- I want my money back so I can go on a shopping spree and Havidol.
Posted by laima on February 16, 2007, at 21:53:03
In reply to Re: Take the DSACDAD online diagnostic test, posted by linkadge on February 16, 2007, at 18:32:07
Artists? Political activist types? Ie, anti-corporate activists?> Who creates a page like this? This would have taken quite some time.
>
> Linkadge
Posted by laima on February 16, 2007, at 22:06:51
In reply to Re: Take the DSACDAD online diagnostic test » linkadge, posted by laima on February 16, 2007, at 21:53:03
Actually, I've seen some similar faux-medication ads in some off-radar art magazines before.
Posted by Quintal on February 16, 2007, at 22:09:36
In reply to Re: Take the DSACDAD online diagnostic test » linkadge, posted by laima on February 16, 2007, at 21:53:03
>Artists? Political activist types? Ie, anti-corporate activists?
No, I don't think so. Just people who have a keen perception of what's going on in psychiatric medicine and a healthy sense of humour.
Q
Posted by laima on February 16, 2007, at 22:51:45
In reply to Re: Take the DSACDAD online diagnostic test, posted by Quintal on February 16, 2007, at 22:09:36
Check it out:
http://en.wikipedia.org/wiki/Havidol
Havidol is a mock advertisement campaign for a fake disorder called Dysphoric Social Attention Consumption Deficit Anxiety Disorder (DSACDAD).
The campaign on display in a New York City art gallery and on a website has far exceeded organizers expectations as thousands of people have contacted them seeking prescription information.
> >Artists? Political activist types? Ie, anti-corporate activists?
>
> No, I don't think so. Just people who have a keen perception of what's going on in psychiatric medicine and a healthy sense of humour.
>
> Q
Posted by laima on February 16, 2007, at 23:01:31
In reply to Re: Take the DSACDAD online diagnostic test » Quintal, posted by laima on February 16, 2007, at 22:51:45
On display now-
and partially indirectly funded by the Australian govt.
Posted by Quintal on February 16, 2007, at 23:08:58
In reply to Re: Take the DSACDAD online diagnostic test » Quintal, posted by laima on February 16, 2007, at 22:51:45
>thousands of people have contacted them seeking prescription information.
Wonders never cease......who could be so mindless as to read through all that and not suspect a ruse? I suppose it could be fairly convincing to people not fluent in psychpharmacology who are heavily sedated.
I wonder what would happen if they were to go round offering free samples to doctors? I would hope otherwise but my experience tells me there would be at least a few who would take the bait.
Q
Posted by River1924 on February 16, 2007, at 23:46:20
In reply to Re: Take the DSACDAD online diagnostic test » laima, posted by Quintal on February 16, 2007, at 23:08:58
Posted by Quintal on February 16, 2007, at 23:51:47
In reply to I love the video... :) (nm), posted by River1924 on February 16, 2007, at 23:46:20
Mine won't play the video for some reason - can only get the audio. Sounds good though.
Q
Posted by River1924 on February 16, 2007, at 23:52:23
In reply to I love the video... :) (nm), posted by River1924 on February 16, 2007, at 23:46:20
Posted by Quintal on February 17, 2007, at 0:04:00
In reply to And the honest 'privacy policy', too. (nm), posted by River1924 on February 16, 2007, at 23:52:23
CONSUMER PRIVACY
Paradise Pharmed and Future Pharms Inc. respects the privacy of visitors to its websites, as a result, we have developed this website privacy policy. This website privacy policy applies only to the operation of websites that directly link to this policy when you click on "privacy statement" in the website footer.
Through this website Paradise Pharmed and Future Pharms Inc. will collect information that can identify you, such as your name, address, telephone number, e-mail address, and other similar information ("Your Information") when it is voluntarily submitted to us (however, see discussion below about "IP Addresses" if you have a broadband connection). We will use Your Information to respond to requests you may make of us, and from time to time, we may refer to Your Information to better understand your needs and how we can improve our websites, products and services. We may also use Your Information to contact you and/or provide you with general health information (like information on certain health conditions) as well as information about our products and services. We may also enhance or merge Your Information with data obtained from third parties for the same purposes.
Any other information transferred by you in connection with your visit to this site ("Other Information" - that is, information that cannot be used to identify you) may be included in databases owned and maintained by Paradise Pharmed and Future Pharms Inc. or its agents. We retains all rights to these databases and the information contained in them. Other Information we collect may include your IP Address and other information gathered through our weblogs and cookies (see below).
This site may use a technology known as web beacons - sometimes called single-pixel gifs - that allow this site to collect web log information. A web beacon is a graphic on a web page or in an e-mail message designed to track pages viewed or messages opened. Web log information is gathered when you visit one of our websites by the computer that hosts our website (called a "webserver"). The webserver automatically recognizes some non-personal information, such as the date and time you visited our site, the pages you visited, the website you came from, the type of browser you are using (e.g., Internet Explorer), the type of operating system you are using (e.g., Windows 2000), and the domain name and address of your Internet service provider (e.g., AOL). We may also include web beacons in promotional e-mail messages in order to determine whether messages have been opened.
This website may use a technology called a "cookie". A cookie is a piece of information that our webserver sends to your computer (actually to your browser file) when you access a website. Then when you come back our site will detect whether you have one of our cookies on your computer. Our cookies help provide additional functionality to the site and help us analyze site usage more accurately. For instance, our site may set a cookie on your browser that keeps you from needing to remember and then enter a password more than once during a visit to the site.
This website uses Internet Protocol (IP) Addresses. An IP Address is a number assigned to your computer by your Internet service provider so you can access the Internet. Generally, an IP address changes each time you connect to the Internet (it is a "dynamic" address). Note, however, that if you have a broadband connection, depending on your individual circumstance, it is possible that your IP Address that we collect, or even perhaps a cookie we use, may contain information that could be deemed identifiable. This is because with some broadband connections your IP Address doesn't change (it is "static") and could be associated with your personal computer. We use your IP address to report aggregate information on use and to help improve the website.
You should be aware that this site is not intended for, or designed to attract, individuals under the age of 18. We do not collect personally identifiable information from any person we actually know is an individual under the age of 18.
Areas of this website that collect Your Information use industry standard secure socket layer encryption (SSL); however, to take advantage of this your browser must support encryption protection (found in Internet Explorer release 3.0 and above).
We may share Your Information with agents, contractors or partners of Paradise Pharmed and Future Pharms Inc. in connection with services that these individuals or entities perform for, or with, Paradise Pharmed and Future Pharms Inc.. These agents, contractors or partners are restricted from using this data in any way other than to provide services for Paradise Pharmed and Future Pharms Inc., or services for the collaboration in which they and Paradise Pharmed and Future Pharms Inc. are engaged (for example, some of our products are developed and marketed through joint agreements with other companies). We may, for example, provide your information to agents, contractors or partners for hosting our databases, for data processing services, or so that they can mail you information that you requested.
Paradise Pharmed and Future Pharms Inc. reserves the right to share Your Information to respond to duly authorized information requests of governmental authorities or where required by law. In exceptionally rare circumstances where national, state or company security is at issue (such as with the World Trade Center terrorist act in September, 2001), Paradise Pharmed and Future Pharms Inc. reserves the right to share our entire database of visitors and customers with appropriate governmental authorities.
We may also provide Your Information to a third party in connection with the sale, assignment, or other transfer of the business of this website to which the information relates, in which case we will require any such buyer to agree to treat Your Information in accordance with this Privacy Policy.As a convenience to our visitors, this Website currently contains links to a number of sites that we believe may offer useful information. The policies and procedures we described here do not apply to those sites. We suggest contacting those sites directly for information on their privacy, security, data collection, and distribution policies.
To be removed from our contact lists, please write to Paradise Pharmed and Future Pharms Inc. at the following address:
info[at]havidol[dot]comOr call Paradise Pharmed and Future Pharms Inc. toll-free at 1-877-HAVIDOL
Please note that you may continue to receive materials while we are updating our lists.
We may update this Web site Privacy Policy from time to time. When we do update it, for your convenience, we will make the updated policy available on this page.
Last Updated: February 8, 2007
__________________________________________________Yes, very refreshing!
Q
Posted by linkadge on February 17, 2007, at 8:19:45
In reply to Havidol FAQ, posted by Quintal on February 16, 2007, at 20:11:36
Oohhh, what a kick to the knees.
--------
Q: I've heard some things recently about "HAVIDOL and suicide". Where can I get more information about that?A: HAVIDOL is not associated with suicide. You may be confusing HAVIDOL with the class of drugs known as SSRIs. SSRIs treat depression. A combined analysis of studies involving 9 antidepressants showed that in people under 18 the risk of suicide was double that for those taking a sugar pill.
-------
Linkadge
Posted by Larry Hoover on February 17, 2007, at 8:21:02
In reply to Re: Take the DSACDAD online diagnostic test » laima, posted by Quintal on February 16, 2007, at 23:08:58
> I wonder what would happen if they were to go round offering free samples to doctors? I would hope otherwise but my experience tells me there would be at least a few who would take the bait.
>
> QWe might finally get a sense of the magnitude of the placebo effect. Notwithstanding some naysayer's arguments, placebo-controlled clinical trials are not comparing an active drug to *just* a sugar pill. All the trappings of qualified medical care and supportive interaction are also supplied. Current practise in clinical trials minimizes the drug effect. In the end, I'm still going to choose something with a 40% chance of working, over one at 30%.
Lar
Posted by laima on February 17, 2007, at 8:23:07
In reply to Re: I love the video... :), posted by Quintal on February 16, 2007, at 23:51:47
Hey Quintal, I discovered that that gallery's website also has a video clip on it- maybe try it and see if it plays better than the one's on havidol.com? It starts by itself here, automatically:http://www.daneyalmahmood.com/justinecooper.html
> Mine won't play the video for some reason - can only get the audio. Sounds good though.
>
> Q
Posted by laima on February 17, 2007, at 9:12:37
In reply to Re: Take the DSACDAD online diagnostic test » Quintal, posted by Larry Hoover on February 17, 2007, at 8:21:02
Looks like a giant Havidol pill is available for purchase- though you may need to contact them to get the price.
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.