natgillin/translations-raw huggingface dataset:
,
Caution is advised in patients taking anticoagulants and/ or medicinal products known to affect platelet function, and in patients with known bleeding tendencies.
.
Discontinuation of treatment Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8).
24%
In a clinical trial adverse events seen on abrupt treatment discontinuation occurred in approximately 44% of patients treated with ARICLAIM and 24% of patients taking placebo.
4. 2).
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more).
#
Hyponatremia may be due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
$
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events).
0 ARICLAIM.
This risk persists until significant remission occurs.
ARICLAIM
Use in children and adolescents under 18 years of age No clinical trials have been conducted with duloxetine in paediatric populations.
18 $(
ARICLAIM should not be used in the treatment of children and adolescents under the age of 18 years.
/
The use of more than one of these products concomitantly should be avoided.
.
Duloxetine should be used with caution in patients treated with other medicinal products associated with hepatic injury.
,
This is most likely to occur within the first few weeks of treatment.
, ARICLAIM
In patients who develop these symptoms, increasing the dose may be detrimental.
(MAO - $.,) - $
Sucrose ARICLAIM gastro-resistant capsules contain sucrose.
),.
5 4.5 Interaction with other medicinal products and other forms of interaction
-
Monoamine oxidase inhibitors (MAOIs): due to the risk of serotonin syndrome, ARICLAIM should not be used in combination with nonselective, irreversible monoamine oxidase inhibitors (MAOIs), or within at least 14 days of discontinuing treatment with an MAOI.
(Hypericum perforatum),
Based on the half-life of duloxetine, at least 5 days should be allowed after stopping ARICLAIM before starting an MAOI (see section 4.3).
%
Caution is advisable if ARICLAIM is used concomitantly with serotonergic antidepressants like SSRIs, tricyclics like clomipramine or amitriptyline, St John’ s wort (Hypericum perforatum), venlafaxine or triptans, tramadol, pethidine and tryptophan.
,
CNS medicinal products: caution is advised when ARICLAIM is taken in combination with other centrally acting medicinal products or substances, including alcohol and sedative medicinal products (benzodiazepines, morphinomimetics, antipsychotics, phenobarbital, sedative antihistamines).
,
The pharmacokinetics of theophylline, a CYP1A2 substrate, were not significantly affected by co-administration with duloxetine (60 mg twice daily).
ARICLAIM
Medicinal products metabolised by CYP2D6:
% CYP2D6.
Duloxetine is a moderate inhibitor of CYP2D6.
(
Caution is advised if ARICLAIM is co-administered with medicinal products that are predominantly metabolised by CYP2D6 (risperidone, tricyclic antidepressants [TCAs] such as nortriptyline, amitriptyline, and imipramine) particularly if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol).
$
Specific in vivo drug interaction studies have not been performed.
ARICLAIM
Anticoagulants and antiplatelet agents:
.
Effects of other medicinal products on duloxetine Antacids and H2 antagonists: co-administration of ARICLAIM with aluminium- and magnesium- containing antacids or with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.
,
Therefore ARICLAIM should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3).
CYP1A2 ARICLAIM
Inducers of CYP1A2:
CYP1A2:, 50%
Population pharmacokinetic studies analyses have shown that smokers have almost 50% lower plasma concentrations of duloxetine compared with non-smokers.
ARICLAIM
6 4.6 Pregnancy and lactation
$
Women should be advised to notify their physician if they become pregnant, or intend to become pregnant, during therapy.
. 3
As the safety of duloxetine in infants is not known, the use of ARICLAIM while breast-feeding is not recommended.
$
4.7 Effects on ability to drive and use machines
$
Patients should be instructed that if they experience sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.
5. 2). +
4.8 Undesirable effects
ARICLAIM
Stress Urinary Incontinence:
4. 7
However, the majority of the most frequent adverse events were mild to moderate and resolved within 30 days of occurrence (e. g. nausea).
1
Table 1:
$
7
3 606
Very
7 976
Common
, 4 370
Uncommon
-
Very Common Uncommon Rare Very
ARICLAIM
Frequency not known
12 -
common
$,
Rare
$-
Investigations Cardiac Disorders
,,
Weight decrease Weight increase Blood cholesterol increased
. *
Creatinine phosphokinase increase
,
Palpitations Nervous System Disorders
958
Tachycardia
955
Supra-ventricular arrhythmia, mainly atrial fibrillation
7
Headache Dizziness Tremor Lethargy Somnolence Paraesthesia
$
Poor quality of sleep Disturbance in attention Nervousness Dysgeusia
(≥1/ 10),
Dyskinesia Myoclonus
(≥1/ 100
Serotonin syndrome Psychomotor restlessness Convulsions AkathisiaExtrapyramidal symptoms
< 1/ 10),
Eye Disorders
(≥1/ 1 000
Blurred vision
< 1/ 100),
Visual disturbance Mydriasis
(≥
Glaucoma
1/ 10 000 < 1/ 1 000), $
Ear and Labyrinth Disorders
)..
Vertigo
(< 1/ 10 000),
Tinnitus1 Ear pain
%
Respiratory, thoracic and mediastinal disorders Gastrointestinal Disorders
! + +
Yawning
%%
Epistaxis Throat tightness
"
Nausea (23.3%) Dry mouth (11.9%) Constipation (10.3%)
+,
Diarrhoea Vomiting Dyspepsia
- $
Gastroenteritis Haematochezia Stomatitis Gastritis Flatulence Eructation Breath odour
4 + #
Gastrointestinal haemorrhage
$
Renals and Urinary Disorders
#
Urinary hesitation Dysuria Nocturia Urine odour abnormal
*.
Urine flow decreased Polyuria
$
Urinary retention
*
Skin and Subcutaneous Tissue Disorders
(, '
Sweating increased
-
Rash Increased tendency to
4
Photo- sensitivity reactions 8
.
Stevens-Johnson Syndrome Angioneurotic oedema
,!
Very
$- 4
Common
* 4 0
Uncommon
4 * 4
Very Common Uncommon Rare Very
-
Frequency not known
(23, 3%)
common
8 * 4 (11, 9%) ((10, 3%)
bruise Night sweats Cold sweat
2 "
Dermatitis contact Urticaria
- &
Rare
*
Muscoskeletal and connective tissue disorders
-
Muscle spasm Muscle tightness Musculo- skeletal pain Trismus
Stevens - Johnson
Muscle twitching
(
Endocrine disorders
,
Hypo- thyroidism Metabolism and Nutrition Disorders
"
Appetite decreased
- $-
Dehydration
$
Hyperglycemia (reported especially in diabetic patients) SIADH Hyponatremia
.
Infections and infestations Laryngitis Vascular Disorders
0
Flushing
-
Syncope2 Blood pressure increase
$$
Hypertensive crisis Orthostatic hypotension2 Peripheral coldness
(
Hypertension
*
General Disorders and Administration Site Conditions Fatigue (10.9%)
(
Abdominal pain Pruritus Weakness Chills
$
Malaise Feeling hot Feeling abnormal Thirst
-
Gait disturbance Feeling cold
+ # 2
Chest pain
1 & "(10, 9%)
Immune system
- 3, $
disorders
-
Hyper- sensitivity disorder
3
Anaphylactic reaction
-
Hepato-biliary disorders
$
Hepatitis3 Elevated liver enzymes (ALT, AST, alkaline phosphatase) Acute liver injury
$
Hepatic failure Jaundice
,
Reproductive System and Breast Disorders Menopausal
,%
9
# - 3
Very
AST,
Common
(ALT,
Uncommon
3
Very Common Uncommon Rare Very
%%)
Frequency not known
) $
common
-
symptoms Gynaecological haemorrhage
* 7,
Rare
1
Psychiatric Disorders 1
$
Insomnia AnxietySlee p disorder Agitation Libido decreased
$
Disorientation Abnormal dreams Apathy Bruxism Orgasm abnormal
4. 4)
Hallucinations
.
Suicidal behaviour Suicidal ideation 4 Mania Aggression and anger 5
$
2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of treatment 3 See section 4.4 4 Cases of suicidal ideation and suicidal behaviours have been reported during duloxetine therapy or early after treatment discontinuation (see section 4.4) 5 Cases of aggression and anger have been reported particularly early in treatment of after treatment discontinuation.
$
It is therefore advised that when duloxetine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
$
The heart rate-corrected QT interval in duloxetine-treated patients did not differ from that seen in placebo-treated patients.
(
There was also a small increase in fasting blood glucose and in total cholesterol in duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care group.
$
The most commonly observed adverse reactions in patients with diabetic neuropathic pain treated with ARICLAIM were: nausea; headache, dry mouth and somnolence.
10)
10 Table 2:
,
Very
SSRIs
Common
SNRIs, $
Uncommon
4. 2
Rare
4. 4).
Very Rare
755
Frequency not
779
common
12 -
known
HbA1 $.
Investigations
HbA1
Weight decrease
.
Weight increase Creatinine phosphokinase increase
,
Blood cholesterol increased
0, 3% - /
Cardiac Disorders
1 964
Palpitations
$).
Tachycardia
(
Supra- ventricular arrhythmia, mainly atrial fibrillation
5 253
Nervous System
, 3 289
Disorders
-
Headache (13.8%) Somnolence (10.7%) Eye Disorders
$/
Dizziness Tremor Lethargy Paraesthesia
$
Dyskinesia Poor quality sleep Nervousness Myoclonus Disturbance in attention Dysgeusia
$.
Serotonin syndrome Convulsions Akathisia Psychomotor restlessness Extra- pyramidal symptoms
ARICLAIM,
Blurred vision
(≥1/ 10),
Visual disturbance Mydriasis
(≥1/ 100
Glaucoma
< 1/ 10),
Ear and Labyrinth Disorders
(≥1/ 1 000
Tinnitus 1
< 1/ 100),
Vertigo Ear pain
(≥ 1/ 10 000
Respiratory, thoracic and mediastinal disorders
< 1/ 1 000),
Yawning
(< 1/ 10 000),
Epistaxis Throat tightness
(
Gastrointestinal
&, +
Disorders
%%
Nausea (21.7%) Dry mouth (13.2%)
+,
Diarrhoea Constipation Vomiting Dyspepsia Flatulence
- $
Gastroenteritis Stomatitis Gastritis Eructation
(13, 8%)
Haematochezia Breath odour
+ #
Gastrointestinal haemorrhage
#
Renals and Urinary Disorders
(
Urinary Retention Urinary hesitation Dysuria Nocturia
(10, 7%)
Urine odour abnormal
11 $
11
5 1 6 0
Very
4 * 4
Rare
(21, 7%)
Very Rare
(13, 2%)
Frequency not
"&%
common
Stevens - Johnson,
Polyuria Urine flow decreased
0
known
-
Skin and Subcutaneous Tissue Disorders
$$
Rash Sweating increased Night sweats
(
Photo- sensitivity reactions Increased tendency to bruise Dermatitis contact Urticaria Cold sweat
*
Stevens- Johnson Syndrome Angio-neurotic oedema
, *
Muscoskeletal and connective tissue disorders
(
Musculo- skeletal pain Muscle tightness Muscle spasm
(ALT,
Muscle twitching
7
Trismus
5
Endocrine disorders Hypo- thyroidism Metabolism and Nutrition Disorders
4. 4.
Decreased Appetite
$
Hyperglycemia (reported especially in diabetic patients)
5
Dehydration SIADH Hypo-natremia
(
Infections and infestations Laryngitis Vascular Disorders
4. 4)
Flushing
.
Syncope2 Orthostatic hypotension2 Blood pressure increase Peripheral coldness
$
Hypertensive crisis Hypertension
$
General Disorders and Administration Site Conditions
$
Fatigue Abdominal pain
(
Feeling hot Malaise Gait disturbance Feeling abnormal Feeling cold Thirst Chills
SSRIs
Chest pain
SNRIs
Immune system disorders
4. 4).
Hyper- sensitivity
HbA1
Anaphylactic reaction
,,
12
, 52,
Very
HbA1
Common
0, 3% -
Uncommon
/ $
Rare
$- $-
Very Rare
QT.
Frequency not
528
common
, $/
disorder
205,
known
QT, PR, QRS
Hepato-biliary disorders
$.
Hepatitis3 Elevated liver enzymes (ALT, AST, alkaline phosphatase)
QTcB
Hepatic failure Jaundice
14 4. 9 &!
Acute liver injury
1 000 mg.
Reproductive System and Breast Disorders
4 800 mg.!
Erectile dysfunction
(
Sexual dysfunction Ejaculation disorder Ejaculation delayed Gynaecological haemorrhage
ATC
Menopausal symptoms
N06AX21
Psychiatric Disorders
(5- HT)
Insomnia
(NE). +
Aggression
5- HT
Suicidal
$% (! ").
Abnormal dreams Anxiety
* $
Sleep disorder Apathy Disorientation
$-) $.
and anger 5 Mania
(I- QOL).
behaviour4 Suicidal ideation4
1 913%
1
(22
AgitationLibid Bruxism o decreased Orgasm abnormal
ARICLAIM,
Hallucinations
$
Cases of tinnitus have also been reported after treatment discontinuation.
9, 2
2 Cases of orthostatic hypotension and syncope have been reported especially at the initiation of treatment.
5, 9,
It is therefore advised that when duloxetine treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
p < 0, 001).
There was also a small increase in fasting blood glucose and in total cholesterol in
,
13 duloxetine-treated patients while those laboratory tests showed a slight decrease in the routine care group.
$
No clinically significant differences were observed for QT, PR, QRS, or QTcB measurements between duloxetine- treated and placebo-treated patients.
$
4.9 Overdose
(PGI),
Signs and symptoms of overdose (duloxetine alone or in combination with other medicinal products) included somnolence, coma, serotonin syndrome, seizures, vomiting and tachycardia.
$p < 0, 001).
A free airway should be established.
,
5.
$(64, 6%
PHARMACOLOGICAL PROPERTIES
50, 1%,
5.1 Pharmacodynamic properties
ARICLAIM
Pharmacotherapeutic group:
ARICLAIM
Other antidepressants.
ARICLAIM
ATC code:
(PFMT):
N06AX21
12 -
It weakly inhibits dopamine reuptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.
,
A similar mechanism in women is believed to result in stronger urethral closure during urine storage with physical stress that could explain the efficacy of duloxetine in the treatment of women with SUI.
,
The pain inhibitory action of duloxetine is believed to be a result of potentiation of descending inhibitory pain pathways within the central nervous system.
, ARICLAIM $
Stress Urinary Incontinence:
.
14 In an additional study limited to patients with severe SUI, all responses with duloxetine were achieved within 2 weeks.
(
In these women, ARICLAIM may provide no benefit beyond that afforded by more conservative behavioural interventions.
ARICLAIM
Quality of Life:
.
ARICLAIM and Prior Continence Surgery: there are limited data that suggest that the benefits of ARICLAIM are not diminished in women with stress urinary incontinence who have previously undergone continence surgery.
:
Combined therapy (duloxetine + PFMT) showed greater improvement in both pad use and condition-specific quality of life measures than ARICLAIM alone or PFMT alone.
, 12 - (22,
Diabetic Peripheral Neuropathic Pain:
88
The difference in mean improvement between the two active treatment arms was not significant.
30% $,
At least 30% reported pain reduction was recorded in approximately 65% of duloxetine treated patients versus 40% for placebo.
26%.
The corresponding figures for at least 50% pain reduction were 50% and 26% respectively.
30%
Clinical response rates in patients experiencing somnolence were 60% on duloxetine and 30% on placebo.
,
Although data from a one-year open label study offer some evidence for longer-term efficacy, no conclusive efficacy data for treatments longer than 12 weeks duration are available from placebo- controlled studies.
CYP2D6), $
15 5.2 Pharmacokinetic properties
CYP2D6.
Duloxetine is administered as a single enantiomer.
*
Duloxetine is well absorbed after oral administration with a Cmax occurring 6 hours post dose.
32%
The absolute oral bioavailability of duloxetine ranged from 32% to 80% (mean of 50%; N=8 subjects).
6 10
Food delays the time to reach the peak concentration from 6 to 10 hours and it marginally decreases the extent of absorption (approximately 11%).
96%
Duloxetine is approximately 96% bound to human plasma proteins.
CYP2D6 CYP1A2
Duloxetine binds to both albumin and alpha-1 acid glycoprotein.
$
The pharmacokinetics of duloxetine in patients who are poor metabolisers with respect to CYP2D6 has not been specifically investigated.
/. in vitro
Limited data suggest that the plasma levels of duloxetine are higher in these patients.
4 -
After an intravenous dose the plasma clearance of duloxetine ranges from 22 l/ hr to 46 l/ hr (mean of 36 l/ hr) After an oral dose the apparent plasma clearance of duloxetine ranges from 33 to 261 l/ hr (mean 101 l/ hr).
'%: #
Special populations:
50%
Gender: pharmacokinetic differences have been identified between males and females (apparent plasma clearance is approximatively 50% lower in females).
-
As a general recommendation, caution should be exercised when treating the elderly (see sections 4.2 and 4.4).
6,
Pharmacokinetic data on duloxetine is limited in patients with mild or moderate renal impairment.
,
The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic insufficiency.
$
Lactation did not influence duloxetine pharmacokinetics.
-
16 5.3 Preclinical safety data
–
The underlying mechanism and the clinical relevance are unknown.
.
In pre/ postnatal toxicity study in the rat, duloxetine induced adverse behavioural effects in the offspring at systemic exposures levels below maximum clinical exposure (AUC).
:
6.
(≥65 25%
PHARMACEUTICAL PARTICULARS
) (AUC
6.1 List of excipients
25%,),
Capsule content:
4. 4).
Hypromellose.
:
Capsule shell:
:
Edible Ink:
(Child Pugh Class B),
6.2 Incompatibilities
2, 3. 2
Not applicable.
, AUC 3, 7 - $
6.3 Shelf life
.
3 years.
17
17 6.4 Special precautions for storage
(E132)
Store in the original package in order to protect from moisture.
30°C.
Do not store above 30°C.
(PCTFE) $
6.5 Nature and contents of container
)
Polyvinylchloride (PVC), Polyethylene (PE), and Polychlorotrifluoroethylene (PCTFE) blister sealed with an aluminum foil.
28, 56, 98, 140
Packs of 28, 56, 98, 140 and 196 (2x98) capsules.
196 (2x98)
Not all pack sizes may be marketed.
.
6.6 Special precautions for disposal
! / # 0 "
No special requirements.
Eli Lilly Nederland BV, Grootslag 1- 5, NL- 3991 RA Houten, 0
Eli Lilly Nederland BV, Grootslag 1-5, NL-3991 RA Houten, The Netherlands.
EU/ 1/ 04/ 283/ 002 EU/ 1/ 04/ 283/ 003 EU/ 1/ 04/ 283/ 004 EU/ 1/ 04/ 283/ 005 EU/ 1/ 04/ 283/ 006
EU/ 1/ 04/ 283/ 002 EU/ 1/ 04/ 283/ 003 EU/ 1/ 04/ 283/ 004 EU/ 1/ 04/ 283/ 005 EU/ 1/ 04/ 283/ 006
11
11 August 2004
6
10.
ARICLAIM 20 mg
ARICLAIM 20 mg hard gastro-resistant capsules.
20 mg
Each capsule contains 20 mg of duloxetine (as hydrochloride).
5, 7 mg.
Excipients: sucrose 5.7 mg.
ARICLAIM (.
PHARMACEUTICAL FORM
ARICLAIM.
Hard gastro-resistant capsule.
20
Opaque blue body, imprinted with ‘ 20 mg’ and an opaque blue cap, imprinted with ‘ 9544’.
. &
4.
.
4.1 Therapeutic indications
,
Treatment of diabetic peripheral neuropathic pain in adults.
,
4.2 Posology and method of administration
.
Dose escalation may decrease, though not eliminate, the risk of nausea and dizziness.
ARICLAIM 20 mg
However, limited data are available to support the efficacy of ARICLAIM 20 mg twice daily.
5. 1).
Additional response after this time is unlikely (see 5.1).
+
The therapeutic benefit should regularly (at least every three months) be reassessed.
ARICLAIM $
Hepatic insufficiency:
4. 3).
Renal insufficiency:
ARICLAIM,
Elderly:
ARICLAIM
Children and adolescents:
4. 5).
There is no experience in children (see section 4.4).
CYP1A2,
4.3 Contraindications
%
Hypersensitivity to the active substance or to any of the excipients.
,
Liver disease resulting in hepatic impairment (see section 5.2).
%
ARICLAIM should not be used in combination with nonselective, irreversible Monoamine Oxidase Inhibitors - MAOIs (see section 4.5).
,
ARICLAIM should not be used in combination with CYP1A2 inhibitors, like fluvoxamine, ciprofloxacin or enoxacine since the combination results in elevated plasma concentrations of duloxetine (see section 4.5).
< 30 ml/ min)
Severe renal impairment (creatinine clearance < 30 ml/ min) (see section 4.4).
(.
The initiation of treatment with ARICLAIM is contraindicated in patients with uncontrolled hypertension that could expose patients to a potential risk of hypertensive crisis (see sections 4.4 and 4.8).
ARICLAIM, (
4.4 Special warnings and precautions for use
.
Mania and Seizures ARICLAIM should be used with caution in patients with a history of mania or a diagnosis of bipolar disorder, and/ or seizures.
4. 4
Use with antidepressants The use of ARICLAIM in combination with antidepressants (especially with SSRI, SNRI and reversible MAOIs) is not recommended (see below “ Depression, suicidal ideation and behaviour” and Section 4.5).
4. 8).
20 St John’ s wort Undesirable effects may be more common during concomitant use of ARICLAIM and herbal preparations containing St John’ s wort (Hypericum perforatum).
21 4. 4
Mydriasis Mydriasis has been reported in association with duloxetine, therefore, caution should be used when prescribing duloxetine in patients with increased intraocular pressure, or those at risk of acute narrow- angle glaucoma.
% #
For patients who experience a sustained increase in blood pressure while receiving duloxetine either dose reduction or gradual discontinuation should be considered (see section 4.8).
$$
Caution is advised in patients taking anticoagulants and/ or medicinal products known to affect platelet function, and in patients with known bleeding tendencies.
4. 2.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more).
*
Caution is required in patients at increased risk for hyponatremia; such as elderly, cirrhotic, or dehydrated patients or patients treated with diuretics.
(SNRIs).
Hyponatremia may be due to a syndrome of inappropriate anti-diuretic hormone secretion (SIADH).
,
If a decision to initiate antidepressant pharmacological therapy is taken, the gradual discontinuation of ARICLAIM is recommended (see Section 4.2).
.
Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
%
The use of more than one of these products concomitantly should be avoided.
$
Duloxetine should be used with caution in patients treated with other medicinal products associated with hepatic injury.
,
In patients who develop these symptoms, increasing the dose may be detrimental.
$/
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.
22
22 4.5 Interaction with other medicinal products and other forms of interaction
. +
Based on the half-life of duloxetine, at least 5 days should be allowed after stopping ARICLAIM before starting an MAOI (see section 4.3).
$
Caution is advisable if ARICLAIM is used concomitantly with serotonergic antidepressants like SSRIs, tricyclics like clomipramine or amitriptyline, St John’ s wort (Hypericum perforatum), venlafaxine or triptans, tramadol, pethidine and tryptophan.
,
Specific in vivo drug interaction studies have not been performed.
(
Effects of other medicinal products on duloxetine Antacids and H2 antagonists: co-administration of ARICLAIM with aluminium- and magnesium- containing antacids or with famotidine had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose.
.
Therefore ARICLAIM should not be administered in combination with potent inhibitors of CYP1A2 like fluvoxamine (see section 4.3).
ARICLAIM
Inducers of CYP1A2:
23
23 4.6 Pregnancy and lactation
$$.
Studies in animals have shown reproductive toxicity at systemic exposure levels (AUC) of duloxetine lower than the maximum clinical exposure (see section 5.3).
(MAO - $.,) - $
The potential risk for humans is unknown.
),.
As the safety of duloxetine in infants is not known, the use of ARICLAIM while breast-feeding is not recommended.
-
4.7 Effects on ability to drive and use machines
14
Patients should be instructed that if they experience sedation or dizziness they should avoid potentially hazardous tasks such as driving or operating machinery.
ARICLAIM
4.8 Undesirable effects
,
The data analysis of four 12-week, placebo-controlled clinical trials in patients with SUI, including 958 duloxetine-treated and 955 placebo-treated patients, showed that the onset of the reported adverse events typically occurred in the first week of therapy.