importance, sufficient time must elapse before initiating TCA treatment in a
1 Includes reports of "dry lips", "dry throat", and "thirst"
patient being withdrawn from fluoxetine, given the long halflife of the parent
2 Includes reports of "pruritus exacerbated"
and active metabolite (at least 5 weeks may be necessary).
3 Includes report of "increased irritation at application site"
Concomitant use of tricyclic antidepressants with drugs that can inhibit
4 Includes reports of "lightheadedness" and "dizziness/vertigo"
cytochrome P450 2D6 may require lower doses than usually prescribed for
5 Includes reports of "bitter taste" and "metallic taste in mouth"
either the tricyclic antidepressant or the other drug. It is desirable to monitor
TCA plasma levels whenever a TCA is going to be co-administered with
Adverse events occurring in 0.5% to < 1.0% of PRUDOXIN™ Cream
another drug known to be an inhibitor of P450 2D6.
treated patients in the controlled clinical trials included: nervousness/
PRUDOXIN™ (doxepin hydrochloride) CREAM, 5%
anxiety, tongue numbness, fever, and nausea.
FOR TOPICAL DERMATOLOGIC USE ONLY —
Serious side effects and even death have been reported fol-
NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.
lowing the concomitant use of certain drugs with MAO inhibitors. Therefore,
MAO inhibitors should be discontinued at least two weeks prior to the cau-
Twenty-six cases of allergic contact dermatitis have been reported in
tious initiation of therapy with PRUDOXIN™ Cream. The exact length of time
patients using PRUDOXIN™ Cream, twenty of which were documented
may vary and is dependent upon the particular MAO inhibitor being used, the
by positive patch test to doxepin 5% cream.
PRUDOXIN™ (doxepin hydrochloride) Cream, 5% is a topical cream. Each gram
length of time it has been administered, and the dosage involved.
contains: 50 mg of doxepin hydrochloride (equivalent to 44.3 mg of doxepin).
Serious anticholinergic symptoms (i.e., severe dry mouth,
Deaths may occur from overdosage with this class of drugs. As the
management is complex and changing, it is recommended that the
Doxepin hydrochloride is one of a class of agents known as dibenzoxepin tricyclic
urinary retention and blurred vision) have been associated with elevations in
physician contact a poison control center for current information on
antidepressant compounds. It is an isomeric mixture of N,N-dimethyldibenz[b,e
the serum levels of tricyclic antidepressants when cimetidine therapy is initi-
treatment. Signs and symptoms of toxicity develop rapidly after tricyclic
oxepin-Δ11(6H),γ-propylamine hydrochloride. Doxepin hydrochloride has an
ated. Additionally, higher than expected tricyclic antidepressant levels have
antidepressant overdose; therefore, hospital monitoring is required as
empirical formula of C19H21NO•HCl and a molecular weight of 316.
been observed when they are begun in patients already taking cimetidine.
soon as possible.
Alcohol ingestion may exacerbate the potential sedative effects of
PRUDOXIN™ Cream. This is especially important in patients who may use
Should overdosage with topical application of PRUDOXIN™ Cream
occur, the signs and symptoms may include: cardiac dysrhythmias,
A case of severe hypoglycemia has been reported in a type
severe hypotension, convulsions, and CNS depression, including coma.
II diabetic patient maintained on tolazamide (1 gm/day) 11 days after the
Changes in the electrocardiogram, particularly in QRS axis or width, are
addition of oral doxepin (75 mg/day).
clinically significant indicators of tricyclic antidepressant toxicity.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Other signs of overdose may include: confusion, disturbed concentra-
Carcinogenesis, mutagenesis, and impairment of fertility studies have not
tion, transient visual hallucinations, dilated pupils, agitation, hyperactive
been conducted with doxepin hydrochloride.
reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hy-
PRUDOXIN™ Cream also contains sorbitol, cetyl alcohol, isopropyl myristate,
Pregnancy Category B:
Reproduction studies have been performed in which
perpyrexia, or any of the symptoms listed under ADVERSE REACTIONS.
glyceryl stearate, PEG-100 stearate, petrolatum, benzyl alcohol, titanium dioxide
doxepin was orally administered to rats and rabbits at doses up to 0.6 and
and purified water.
1.2 times, respectively, the estimated exposure to doxepin that results from
Obtain an ECG and immediately initiate cardiac monitoring.
use of 16 grams of PRUDOXIN™ Cream per day (four applications of four grams
Protect the patient's airway, establish an intravenous line and initiate
Although doxepin HCl does have H
of cream per day; dose multiples reflect comparisons made following nor-
gastric decontamination. A minimum of six hours of observation with
1 and H2 histamine receptor blocking actions,
the exact mechanism by which doxepin exerts its antipruritic effect is unknown.
malization of the data on the basis of body surface area estimates) and have
cardiac monitoring and observation for signs of CNS or respiratory de-
PRUDOXIN™ Cream can produce drowsiness which may reduce awareness, includ-
revealed no evidence of harm to rat or rabbit fetuses due to doxepin. There
pression, hypotension, cardiac dysrhythmias and/or conduction blocks,
ing awareness of pruritic symptoms. In 19 pruritic eczema patients treated with
are, however, no adequate and well-controlled studies in pregnant women.
and seizures is strongly advised. If signs of toxicity occur at any time
PRUDOXIN™ Cream, plasma doxepin concentrations ranged from nondetectable to
Because animal reproduction studies are not always predictive of human
during this period, extended monitoring is recommended. There are case
47 ng/mL from percutaneous absorption. Plasma levels from topical application of
response, this drug should be used during pregnancy only if clearly needed.
reports of patients succumbing to fatal dysrhythmias late after overdose;
PRUDOXIN™ Cream can result in CNS and other systemic side effects.
these patients had clinical evidence of significant poisoning prior to
death and most received inadequate gastrointestinal decontamination.
Once absorbed into the systemic circulation, doxepin undergoes hepatic metabolism
Doxepin is excreted in human milk after oral administration. It is possible
Monitoring of plasma drug levels should not guide management of the
that results in conversion to pharmacologically-active desmethyldoxepin. Further
that doxepin may also be excreted in human milk following topical applica-
glucuronidation results in urinary excretion of the parent drug and its metabolites.
tion of PRUDOXIN™ Cream.
Desmethyldoxepin has a half-life that ranges from 28 to 52 hours and is not
One case has been reported of apnea and drowsiness in a nursing infant
A maximal limb-lead QRS duration of ≥ 0.10 seconds
affected by multiple dosing. Plasma levels of both doxepin and desmethyldoxepin
whose mother was taking an oral dosage form of doxepin HCl.
may be the best indication of the severity of the overdose. Intravenous
are highly variable and are poorly correlated with dosage. Wide distribution occurs
sodium bicarbonate should be used to maintain the serum pH in the
in body tissues including lungs, heart, brain, and liver. Renal disease, genetic
Because of the potential for serious adverse reactions in nursing infants
range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation
factors, age, and other medications affect the metabolism and subsequent
from doxepin, a decision should be made whether to discontinue nursing
may also be used. Concomitant use of hyperventilation and sodium
elimination of doxepin. (See PRECAUTIONS - Drug Interactions.)
or to discontinue the drug, taking into account the importance of the drug
bicarbonate should be done with extreme caution, with frequent pH
to the mother.
monitoring. A pH >7.60 or a pCO
INDICATIONS AND USAGE
2 < 20 mm Hg is undesirable. Dysrhyth-
mias unresponsive to sodium bicarbonate therapy/hyperventilation may
PRUDOXIN™ Cream is indicated for the short-term (up to 8 days) management
respond to lidocaine, bretylium or phenytoin. Type 1A and 1C antiar-
of moderate pruritus in adult patients with atopic dermatitis or lichen simplex
The use of PRUDOXIN™ Cream in pediatric patients is not recommended.
rhythmics are generally contraindicated (e.g., quinidine, disopyramide,
chronicus. (See DOSAGE AND ADMINISTRATION.)
Safe conditions for use of PRUDOXIN™ Cream in children have not been
established. One case has been reported of a 2.5-year-old child who
developed somnolence, grand mal seizure, respiratory depression, ECG
In rare instances, hemoperfusion may be beneficial in acute refractory
Because doxepin HCl has an anticholinergic effect and because significant plasma
abnormalities, and coma after treatment with PRUDOXIN™ Cream. A total of
cardiovascular instability in patients with acute toxicity. However, hemo-
levels of doxepin are detectable after topical PRUDOXIN™ Cream application, the
27 grams had been applied over three days for eczema. He was treated with
dialysis, peritoneal dialysis, exchange transfusions, and forced diuresis
use of PRUDOXIN™ Cream is contraindicated in patients with untreated narrow
supportive care, activated charcoal, and systemic alkalization and recovered.
generally have been reported as ineffective in tricyclic antidepressant
angle glaucoma or a tendency to urinary retention.
PRUDOXIN™ Cream is contraindicated in individuals who have shown previous
Clinical studies of PRUDOXIN™ Cream did not include sufficient numbers
In patients with CNS depression, early intubation is advised
sensitivity to any of its components.
of subjects aged 65 and over to determine whether they respond differently
because of the potential for abrupt deterioration. Seizures should
from younger subjects. Other reported clinical experience has not identified
be controlled with benzodiazepines, or if these are ineffective, other
Drowsiness occurs in over 20% of patients treated with PRUDOXIN™ Cream,
differences in responses between the elderly and younger patients. In
anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not
especially in patients receiving treatment to greater than 10% of their body surface
general, dose selection for an elderly patient should be cautious, usually
recommended except to treat life-threatening symptoms that have been
area. Patients should be warned about the possibility of sedation and cautioned
starting at the low end of the dosing range, reflecting the greater frequency
unresponsive to other therapies, and then only in consultation with a
against driving a motor vehicle or operating hazardous machinery while being
of decreased hepatic, renal or cardiac function, and of concomitant disease
poison control center.
treated with PRUDOXIN™ Cream.
or other drug therapy.
The principles of management of child and adult
The sedating effects of alcoholic beverages, antihistamines, and other CNS depres-
The extent of renal excretion of doxepin has not been determined. Because
overdosages are similar. It is strongly recommended that the physician
sants may be potentiated when PRUDOXIN™ Cream is used.
elderly patients are more likely to have decreased renal function, care should
contact the local poison control center for specific pediatric treatment.
be taken in dose selections.
If excessive drowsiness occurs it may be necessary to reduce the frequency of
DOSAGE AND ADMINISTRATION
applications, the amount of cream applied, and/or the percentage of body surface
Sedating drugs may cause confusion and oversedation in the elderly; elderly
A thin film of PRUDOXIN™ Cream should be applied four times each
area treated, or discontinue the drug. However, the efficacy with reduced frequency
patients generally should be observed closely for confusion and overseda-
day with at least a 3 to 4 hour interval between applications. There
of applications has not been established.
tion when started on PRUDOXIN™ Cream. (See WARNINGS.) An 80-year-old
are no data to establish the safety and effectiveness of PRUDOXIN™
male nursing home patient developed probable systemic anticholinergic tox-
Keep this product away from the eyes.
Cream when used for greater than 8 days. Chronic use beyond eight
icity which included urinary retention and delirium after PRUDOXIN™ Cream
days may result in higher systemic levels and should be avoided. Use of
had been applied to his arms, legs and back three times daily for two days.
PRUDOXIN™ Cream for longer than 8 days may result in an increased
likelihood of contact sensitization.
Since drowsiness may occur with the use of PRUDOXIN™ Cream,
Controlled Clinical Trials
patients should be warned of the possibility and cautioned against driving a car
The risk for sedation may increase with greater body surface area
Systemic Adverse Effects:
In controlled clinical trials of patients treated with
or operating dangerous machinery while using this drug. Patients should also be
application of PRUDOXIN™ Cream (See WARNINGS section). Clinical
PRUDOXIN™ Cream, the most common systemic adverse event reported
cautioned that their response to alcohol may be potentiated.
experience has shown that drowsiness is significantly more common
was drowsiness. Drowsiness occurred in 71 of 330 (22%) of patients treated
in patients applying PRUDOXIN™ Cream to over 10% of body surface
Sedating drugs may cause confusion and oversedation in the elderly; elderly
with PRUDOXIN™ Cream compared to 7 of 334 (2%) of patients treated with
area; therefore, patients with greater than 10% of body surface area
patients generally should be observed closely for confusion and oversedation when
vehicle cream. Drowsiness resulted in the premature discontinuation of the
(see WARNINGS section) affected should be particularly cautioned
started on PRUDOXIN™ Cream. (See PRECAUTIONS - Geriatric Use.)
drug in approximately 5% of patients treated with PRUDOXIN™ Cream in
concerning possible drowsiness and other systemic adverse effects of
controlled clinical trials.
Use under occlusion:
Occlusive dressings may increase the absorption of
doxepin. If excessive drowsiness occurs, it may be necessary to do one
most topical drugs; therefore, occlusive dressings should not be utilized with
Local Site Adverse Effects:
In controlled clinical trials of patients treated with
or more of the following: reduce the body surface area treated, reduce
PRUDOXIN™ Cream, the most common local site adverse event reported
the number of applications per day, reduce the amount of cream applied,
was burning and/or stinging at the site of application. These occurred in 76
or discontinue the drug.
Use of PRUDOXIN™ Cream can cause Type IV hypersensitiv-
of 330 (23%) of patients treated with PRUDOXIN™ Cream compared to 54
ity reactions (contact sensitization) to doxepin.
Occlusive dressings may increase the absorption of most topical drugs;
of 334 (16%) of patients treated with vehicle cream. Most of these reactions
therefore, occlusive dressings should not be utilized with PRUDOXIN™
were categorized as "mild"; however, approximately 25% of patients who
Studies have not been performed examining drug interactions with PRUDOXIN™
reported burning and/or stinging reported the reaction as "severe". Four
Cream. However, since plasma levels of doxepin following topical application of
patients treated with PRUDOXIN™ Cream withdrew from the study because
PRUDOXIN™ Cream can reach levels obtained with oral doxepin HCl therapy, the
of the burning and/or stinging.
PRUDOXIN™ Cream is available in a 45 g (NDC 40076-511-45) tube.
following drug interactions are possible following topical PRUDOXIN™ Cream application:
The table below presents the adverse events reported at an incidence of ≥1%
Store at or below 27°C (80°F).
Drugs Metabolized by P450 2D6:
The biochemical activity of the drug metabolizing
in either PRUDOXIN™ or vehicle cream treatment groups during the trials:
isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of
the Caucasian population (about 7-10% of Caucasians are so-called "poor metabo-
lizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity
among Asian, African and other populations are not yet available. Poor metabolizers
have higher than expected plasma concentrations of tricyclic antidepressants
(TCAs) when given usual doses. Depending on the fraction of drug metabolized by
P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold
increase in plasma AUC of the TCA).
Prestium Pharma, Inc.,
Newtown, PA 18940
In addition, certain drugs inhibit the activity of this isozyme and make normal
metabolizers resemble poor metabolizers. An individual who is stable on a given
dosage regimen of a TCA may become abruptly toxic when given one of these
DPT Laboratories, Ltd.
inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450
San Antonio, Texas 78215
Other Application Site Reaction3
2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine)
PRUDOXIN™ is a registered trademark of Delcor Asset Corporation,
and many that are substrates for P450 2D6 (many other antidepressants, phe-
an affiliate of Prestium Pharma, Inc.
nothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all
the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and
2015 Prestium Pharma, Inc.
paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to
which SSRI-TCA interactions may pose clinical problems will depend on the degree
of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution
is indicated in the co-administration of TCAs with any of the SSRIs. Of particular
Educación Basada en la Conciencia Índice de Contenidos Desarrollo del potencial total del estudiante, prevención y tratamiento del estrés, la ansiedad y la © Escuela sin Estrés, 2006. Este programa está respaldado por el País Global de Paz Mundial. Maharishi Mahesh Yogi Fundador de Escuelas de Invencibilidad en todos los países © Escuela sin Estrés, 2006. Este programa está respaldado por el País Global de Paz Mundial.
CIALIS® (tadalafil) FORMES ET PRESENTATIONS CIALIS 2,5 mg comprimés pelliculés. Boîte de 28, sous plaquettes thermoformées. CIALIS 5 mg comprimés pelliculés. Boîte de 28 ou de 84, sous plaquettes thermoformées. CIALIS 10 mg comprimés pelliculés. Boîte de 4, sous plaquettes thermoformées. CIALIS 20 mg comprimés pelliculés. Boîte de 4 ou de 8, sous plaquettes thermoformées. Les comprimés à 2,5 mg sont orange clair-jaune en forme d'amande, avec l'inscription « C 2 ½ » sur l'une des faces. Les comprimés à 5 mg sont jaune clair en forme d'amande, avec l'inscription « C 5 » sur l'une des faces. Les comprimés à 10 mg sont jaune clair en forme d'amande, avec l'inscription « C 10 » sur l'une des faces. Les comprimés à 20 mg sont jaunes en forme d'amande, avec l'inscription « C 20 » sur l'une des faces. COMPOSITION Chaque comprimé de CIALIS 2,5 mg contient 2,5 mg de tadalafil. Chaque comprimé de CIALIS 5 mg contient 5 mg de tadalafil. Chaque comprimé de CIALIS 10 mg contient 10 mg de tadalafil. Chaque comprimé de CIALIS 20 mg contient 20 mg de tadalafil. Excipient à effet notoire : Chaque comprimé pelliculé de CIALIS 2,5 mg contient 87 mg de lactose (sous forme monohydraté). Chaque comprimé pelliculé de CIALIS 5 mg contient 121 mg de lactose (sous forme monohydraté). Chaque comprimé pelliculé de CIALIS 10 mg contient 170 mg de lactose (sous forme monohydraté). Chaque comprimé pelliculé de CIALIS 20 mg contient 233 mg de lactose (sous forme monohydraté). Excipients : Noyau du comprimé : lactose monohydraté, croscarmellose sodique, hydroxypropylcellulose, cellulose microcristalline, laurylsulfate de sodium, stéarate de magnésium. Pelliculage : lactose monohydraté, hypromellose, triacétine, dioxyde de titane (E171), oxyde de fer jaune (E172), talc et uniquement pour CIALIS 2,5 mg : oxyde de fer rouge (E172). INDICATIONS (CIALIS 2,5 mg, 5 mg, 10 mg et 20 mg) : Traitement de la dysfonction érectile chez l'homme adulte. Une stimulation sexuelle est requise pour que le tadalafil soit efficace dans le traitement de la dysfonction érectile. CIALIS n'est pas indiqué chez la femme. (CIALIS 5 mg) : Traitement des signes et symptômes de l'hypertrophie bénigne de la prostate chez l'homme adulte. CIALIS n'est pas indiqué chez la femme. POSOLOGIE ET MODE D'ADMINISTRATION Posologie