natgillin/translations-raw huggingface dataset:
ςησόδ οδεπίπε ωγόλ νε οτ αιγ ςησηφάργογατνυσ ςείροφορηλπ ςιτσ. νωεσήιοποπορτ νώκιδιε αιεγρένειδ ητ αιγ νωεσάτσυσ ςησωπύταιδ ηκγάνα νητ ή ςησηγόλοιξα ςασύοραπ ςητ ςησηίοποπορτ ηκγάνα νητ νυούνκιεδοπυ νεδ ςαίροφολκυκ ςαιεδά ςησηγήροχ ςητ ιατεπέ υοπ ησάφ ητ άτακ νυοτπύκορπ υοπ ανέµοδεδ ατ ιακ νώµικοδ νώκινιλκ ςείροφορηλπ ςενέµηιοποριακιπε ιΟ. υονύδνικ ςαιελέφω ησέχσ ήτκεδοπα εµ ςησηρήτνυσ ιακ ςηξρανέ ησόδ ςω
Rather, the choice of start dose should take into account potential safety concerns in the individual patient based e. g. on sensitivity to adverse reactions and pharmacokinetic considerations.
rosuvastatin (Crestor) 10 mg
In conclusion, the benefit/ risk ratio is favourable for Crestor 5 or Crestor 10 mg as alternative start doses.
ητ αιγ ςαίροφολκυκ αιεδά ίεθηρωχαραπ ιεχέ νώλεµ νώταρκ νωτ ατητόνοιελπ νητσ ςοτνόραπ υοτ αµητράραπ επέλβ ΝΩΙΣΑΜΟΝΟ ΝΩΦΑΝΥΣ ΝΩΤ ΙΑΚ I) (CRESTOR 5 mg ΥΟΤ ΣΗΣΗΓΟΛΟΙΞΑ ΣΗΚΙΝΟΜΗΤΣΙΠΕ ΣΗΤ ΗΨΗΛΙΡΕΠ ΗΚΙΝΕΓ 7
The choice of start dose in the individual patient should take into account aspects of efficacy and safety, as detailed in the SPC.
ίπΕ ΑΤΑΜΣΙΡΟΠ ΑΚΙΝΟΜΗΤΣΙΠΕ
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS
,
Based on the finding that
. ΠΧΠ νητσ ιατνούλανα άτυα
⇒ Crestor 10 mg daily dose leads to a higher reduction in LDL-C compared with 5 mg
, ςαιελάφσα ιακ ςατητόκιταµσελετοπα αταµέθ ηψόπυ ιατνονάβµαλ αν ιεπέρπ ςίενεθσα ςυονέµωνοµεµ εσ ησηγήροχ ςορπ ςηξρανέ ςησόδ ςητ ήγολιπε νητ άταΚ ςηξρανέ ςησόδ ςήκιτκαλλανε ςω
⇒ No important safety or tolerability difference between rosuvastatin 5 mg and 10 mg is evident on the basis of post-marketing or clinical trial data
Crestor 10υοτ ή Crestor 5 mgυοτ ήγολιπε νητ ίεγολοιακιδ υονύδνικ ςαιελέφω ησέχσ η ιτό ιατεγάνυΣ / 8 ΣΟΤΝΟΪΟΡΠ ΥΟΤ ΝΩΚΙΤΣΙΡΗΤΚΑΡΑΧ ΝΩΤ ΗΨΗΛΙΡΕΠ IIΙ ΑΜΗΤΡΑΡΑΠ 9 ήφορτ ςίρωχ ή εµ ςαρέµη ςητ αρώ ετοπήδαιοπο ιατενάβµαλ αν ίεροπµ
The choice of start dose in the individual patient should take into account aspects of efficacy and safety, as detailed in the SPC.
Crestor
6 ANNEX III
όρταιγ όκιδιε όπα ηψελβίπε ιατάτσινυσ
AMENDED SUMMARY OF PRODUCT CHARACTERISTICS OF THE REFERENCE MEMBER STATE
.
7 1.
νωτ ησόδ η ίεθηγηροχ νατΌ ησήρχ 40 mg,
Crestor 5 mg film-coated tablets.
ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ ςέκιδιΕ
Each tablet contains 5 mg rosuvastatin (as rosuvastatin calcium).
οφαργάραπ λβ ςοχγελέ ςόκιδοιρεπ 4. 4
For excipients see 6.1.
(.
3.
ιατίεγρενειδ αν ιεπέρπ αθ ςυοίοπο ςυοτσ ιακ
Film-coated tablet.
εµ οχότσ ςυοτ όκιτυεπαρεθ οτ νυονάχγυτιπε 20 mg,
Round, yellow coloured, intagliated with'ZD4522 'and '5' on one side and plain on the reverse.
),
4.
νωτ ησόδ
4.1 Therapeutic indications
όληψυ ιακ αίµιαλορετσηλοχρεπυ ήραβοσ εµ ςίενεθσα εσ ονόµ ιατεζάτεξε αν ιεπέρπ αθ ητσιγέµ νητσ ησιµθύρ ήκιλετ αιµ ςειεγρένε ςετηµύθιπενΑ
Primary hypercholesterolaemia (type IIa including heterozygous familial hypercholesterolaemia) or mixed dyslipidaemia (type IIb) as an adjunct to diet when response to diet and other non- pharmacological treatments (e. g. exercise, weight reduction) is inadequate.
40 mg,
Homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid lowering treatments (e. g.
), ραπ λβ ςιεσόδ ςερετόληµαχ
LDL apheresis) or if such treatments are not appropriate.
ςιτ εµ ησιρκγύσ εσ
4.2 Posology and method of administration
νωτ ησόδ νητ εµ νώιεγρενε νωτηµύθιπενα ςάροφανα ςατητόνχυσ ςηνέµηξυα 40 mg
Before treatment initiation the patient should be placed on a standard cholesterol-lowering diet that should continue during treatment.
ςητ ωγόΛ ςετητόιδι ςέκιµανυδοκαµραΦ
The dose should be individualised according to the goal of therapy and patient response, using current consensus guidelines.
οφαργάραπ λβ οτητίαραπα ιανίε νάε ςεδάµοδβε
The recommended start dose is 5 or 10 mg orally once daily in both statin naïve or patients switched from another HMG CoA reductase inhibitor.
. ςατνονάβµαλ ήνεθσα υοτ ησιρκόπατνα νητ ιακ ςαίεπαρεθ ςητ οχότσ νοτ εµ αγολάνα ιατεύεκιµοταξε, αν ιεπέρπ ησόδ Η ςαίεπαρεθ ςητ αιεκράιδ ητ άτακ ιεζίχενυσ αν ιεπέρπ αίοπο νητ ατιαίδ
A dose adjustment to the next dose level can be made after 4 weeks, if necessary (see Section 5.1 Pharmacodynamic properties).
. ήκιµιαλορετσηλοχοπυ ηνέµωρειθακ νητσ ίεθετ αν ιεπέρπ αθ ςήνεθσα ο ςαίεπαρεθ ςητ ηξρανέ νητ νιρΠ
In light of the increased reporting rate of adverse reactions with the 40 mg dose compared to lower doses (see Section 4.8 Undesirable effects), a final titration to the maximum dose of 40 mg should only be considered in patients with severe hypercholesterolaemia at high cardiovascular risk (in particular those with familial hypercholesterolaemia), who do not achieve their treatment goal on 20 mg, and in whom routine follow- up will be performed (see Section 4.4 Special warnings and precautions).
ςησηγήροχ ςοπόρτ ιακ αίγολοσο∆
Specialist supervision is recommended when the 40 mg dose is initiated.
ςητ ησερίαφα χ π
Crestor may be given at any time of day, with or without food.
αιδίπιλ ατ νυονώιεµ υοπ νώγωγα LDL
Paediatric use Safety and efficacy have not been established in children.
νώκιτυεπαρεθ νωλλά ιακ ςατιαίδ ςητ αµωρήλπµυσ ςω αίµιαλορετσηλοχρεπυ ςήνεγοκιο ηγυζόµΟ,
Paediatric experience is limited to a small number of children (aged 8 years or above) with homozygous familial hypercholesterolaemia.
ςήκραπε ιανίε νεδ ςυοράβ ύοκιταµωσ.
Therefore, Crestor is not recommended for paediatric use at this time.
η νατό ςατιαίδ ςητ αµωρήλπµυσ ςω ΙΙ υοπύτ αίµιαδιπιλσυδ ήτκιµ ή ςαίµιαλορετσηλοχρεπυ
8 Use in the elderly A start dose of 5 mg is recommended in patients > 70 years (see section 4.4 Special warnings and precautions for use).
ςιεξίεδνε ςέκιτυεπαρεΘ
No other dose adjustment is necessary in relation to age.
ΣΕΙΡΟΦΟΡΗΛΠ ΣΕΚΙΝΙΛΚ ηλλά νητσ ησωπύτκε αίµακ.
Dosage in patients with renal insufficiency No dose adjustment is necessary in patients with mild to moderate renal impairment.
ιακ ηψό αίµ νητσ
The recommended start dose is 5 mg in patients with moderate renal impairment (creatinine clearance < 60 ml/ min).
ησωπύτκε νητ εµ
The 40 mg dose is contraindicated in patients with moderate renal impairment.
ΗΦΡΟΜ ΗΚΙΝΧΕΤΟΚΑΜΡΑΦ 6. 1. οφαργάραπ λβ αχοδκέ ατ
The use of Crestor in patients with severe renal impairment is contraindicated for all doses.
rosuvastatin calcium).
(See Section 4.3 Contraindications and Section 5.2 Pharmacokinetic properties).
ΗΣΕΘΝΥΣ ΗΚΙΤΟΣΟΠ ΙΑΚ ΗΚΙΤΟΙΟΠ οινέµυ ότπελ εµ ανέµµυλακιπε αίκσιδ
Dosage in patients with hepatic impairment There was no increase in systemic exposure to rosuvastatin in subjects with Child-Pugh scores of 7 or below.
εσ νυοτέθαιδορπ υοπ ςετνογάραπ εµ ςίενεθσα εσ ιατυνκίεδνετνα ςηψηλλύσιτνα αρτέµ αληλλάτακ.
However, increased systemic exposure has been observed in subjects with Child-Pugh scores of 8 and 9 (see Section 5.2 Pharmacokinetic properties).
νυονάβµαλ εδ υοπ αίκιλη ήκιγωγαραπανα εσ ςεκίανυγ εσ ιακ αίχυολαγ ιακ ησηύκ νητ άτακ ηνίροπσολκυκ ανορχότυατ νυονάβµαλ υοπ ςίενεθσα εσ
There is no experience in subjects with Child-Pugh scores above 9.
αιεθάπουµ εµ ςίενεθσα εσ ςηνίνιταερκ ησραθάκ αίγρυοτιελσυδ ήκιρφεν ήραβοσ εµ ςίενεθσα εσ
Crestor is contraindicated in patients with active liver disease (see Section 4.3 Contraindications).
(ςήµιτ ςήκιγολοισυφ ςητ υοίρο υοτατώνα υοτ οισάλπιρτ οτ ιενίαβρεπυ. υοπ ύορο υοτ νώσανιµασναρτ νωτ ςησηξύα ετοπήδσαιοπο ιακ ύορο υοτ νώσανιµασναρτ νωτ
Race Increased systemic exposure has been seen in Japanese and Chinese subjects (see section 4.4 Special warnings and special precautions for use and section 5.2 Pharmacokinetic properties).
νωεσήξυα νωνοµίπε νωτηγήξενα νωνέµοναβµαλιρεπµυσ οσόν ήκιταπη όγρενε εµ ςίενεθσα εσ
The recommended start dose is 5 mg for patients of Japanese and Chinese ancestry.
αχοδκέ ατ όπα οιοπάκ εσ ή
The 40 mg dose is contraindicated in Japanese and Chinese patients (see sections 4.3 Contraindications and 5.2 Pharmacokinetic properties).
ητσ αίσηθσιαυερεπυ εµ ςίενεθσα εσ rosuvastatin
Dosage in patients with pre-disposing factors to myopathy The recommended start dose is 5 mg in patients with predisposing factors to myopathy (see Section 4.4 Special warnings and special precautions for use).
λβ ςίενεθσα ςυοτ ςύοτυα εσ ιατυνκίεδνετνα 4. 3 (.
The 40 mg dose is contraindicated in some of these patients (see Section 4.3 Contraindications).
νωτ ησόδ Η
4.3 Contraindications
οφαργάραπ επέλβ
Crestor is contraindicated:
mg (
- -
5 ιανίε αιεθάπουµ εσ νυοτέθαιδορπ υοπ ςετνογάραπ εµ ςίενεθσα ςυοτ αιγ ςηξρανέ ησόδ ηνεµώτσινυσ Η αιεθάπουµ εσ νυοτέθαιδορπ υοπ ςετνογάραπ εµ ςίενεθσα εσ αίγολοσο∆ ςετητόιδι ςέκιτηνικοκαµραΦ
in patients with hypersensitivity to rosuvastatin or to any of the excipients. in patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 x the upper limit of normal (ULN).
).
- - - -
οφαργάραπ ιακ ςιεξίεδνετνΑ
in patients with severe renal impairment (creatinine clearance < 30 ml/ min). in patients with myopathy. in patients receiving concomitant cyclosporin. during pregnancy and lactation and in women of childbearing potential not using appropriate contraceptive measures.
ςυοζένιΚ ιακ ςενωπάΙ εσ ιατυνκίεδνετνα
The 40 mg dose is contraindicated in patients with pre-disposing factors for myopathy/ rhabdomyolysis.
νωτ ησόδ Η
Such factors include:
5 mg.
- - - - - - - -
4. 4οφαργάραπ λβ ςυοζένιΚ ιακ ςενωπάΙ εσ ησεθκέ ήκιταµητσυσ ηνέµηξυα ίεθηρηταραπ ιεχΈ (. ήλυΦ
moderate renal impairment (creatinine clearence < 60 ml/ min) hypothyroidism personal or family history of hereditary muscular disorders previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate alcohol abuse situations where an increase in plasma levels may occur Japanese and Chinese patients concomitant use of fibrates.
εµ αµοτά εσ αίριεπµε ιεχράπυ νε∆ ησήρχ ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ).
(See sections 4.4 Special warnings and special precautions for use, 4.5 Interaction with other medicinal products and other forms of interaction and 5.2 Pharmacokinetic properties).
ςέκιδιΕ
4.4 Special warnings and special precautions for use
αθ ςίενεθσα ςυοτ ςύοτυα εΣ ςετητόιδι ςέκιτηνικοκαµραΦ
Renal Effects Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with higher doses of Crestor, in particular 40 mg, where it was transient or intermittent in most cases.
οφαργάραπ λβ ιακ
Proteinuria has not been shown to be predictive of acute or progressive renal disease (see Section 4.8 Undesirable effects).
ησηγόλοµθαβ εµ αµοτά εσ οφαργάραπ ιακ ςιεξίεδνετνΑ
An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40 mg.
εσ ςησεθκέ ςήκιταµητσυσ ςητ ησηξύα εξρήπυ νε∆ rosuvastatin αίγρυοτιελσυδ ήκιταπη εµ ςίενεθσα εσ αίγολοσο∆ ςετητόιδι ςέκιτηνικοκαµραΦ).
Skeletal Muscle Effects Effects on skeletal muscle e. g. myalgia, myopathy and, rarely, rhabdomyolysis have been reported in Crestor-treated patients with all doses and in particular with doses > 20 mg.
αιεκράπενα ήκιρφεν ήραβοσ εµ ςίενεθσα εσ
Creatine Kinase Measurement Creatine Kinase (CK) should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase which may confound interpretation of the result.
υοτ ησήρχ Η αιεκράπενα ήκιρφεν αιρτέµ εµ Crestor
If CK levels are significantly elevated at baseline (> 5xULN) a confirmatory test should be carried out within 5 – 7 days.
αίκιλη νητ εµ ησέχσ εσ ςαίγολοσοδ
If the repeat test confirms a baseline CK > 5xULN, treatment should not be started.
ςητ ήγοµρασορπ ηλλά ιατίετιαπα νε∆ ησήρχ ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ).
Before Treatment Crestor, as with other HMG-CoA reductase inhibitors, should be prescribed with caution in patients with pre-disposing factors for myopathy/ rhabdomyolysis.
ςέκιδιΕ
Such factors include:
οφαργάραπ λβ νώτε 4. 4
- renal impairment
(. > 70
- hypothyroidism
5 mg ςυονέµωικιλη εσ ησηγήροΧ
- personal or family history of hereditary muscular disorders
οτ ότυα ογόλ οτ αιΓ αίµιαλορετσηλοχρεπυ Crestor,
- previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate
ηξρανέ νητ (> 5 x ULN),
- alcohol abuse
> 70
- age > 70 years
λόοκλα ησηρχάτακ ητάρπµιφ ή
- situations where an increase in plasma levels may occur (see section 5.2 Pharmacokinetic
αν ιεπέρπ
properties)
οτ ςησάγωγανα
- concomitant use of fibrates.
ςητ ςίελοτσανα ςυολλά ςυοτ εµ ιακ ςωπΌ HMG- CoA αίεπαρεθ ητ νιρΠ
In such patients the risk of treatment should be considered in relation to possible benefit and clinical monitoring is recommended.
αθ (> 5xULN)
If CK levels are significantly elevated at baseline (> 5xULN) treatment should not be started.
ςητ αδεπίπε ατ νάΕ νωτάµσελετοπα CK
Whilst on Treatment Patients should be asked to report inexplicable muscle pain, weakness or cramps immediately, particularly if associated with malaise or fever.
ήκιτκαλλανε ηγολύε CK,
CK levels should be measured in these patients.
ησάνικ ήκινιταερκ Η (CK)
Therapy should be discontinued if CK levels are markedly elevated (> 5xULN) or if muscular symptoms are severe and cause daily discomfort (even if CK levels are 5x ULN).
ςησάνικ ςήκινιταερκ ςητ ησηρτέΜ > 20 mg. ςιεσόδ εµ αρετίαιδι ιακ ςιεσόδ ςιτ ςελό εµ αινάπσ ιακ αιεθάπουµ αίγλαυµ χ π,
If symptoms resolve and CK levels ≤ return to normal, then consideration should be given to re-introducing Crestor or an alternative HMG- CoA reductase inhibitor at the lowest dose with close monitoring. Routine monitoring of CK levels in asymptomatic patients is not warranted.
εµ αίεπαρεθ ναβαλέ υοπ ςίενεθσα εσ ησυλόυµοδβαρ Crestor ςεύµ ςύοκιτελεκσ ςυοτσ ςιεσάρδιπε ίεθρεφανα νυοχΈ,.. ςυµ ςύοκιτελεκσ ςυοτσ ςιεσάρδιπΕ ησόδ νυονάβµαλ υοπ νώνεθσα νωτ νωχγέλε 40 mg.
However, an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives including gemfibrozil, cyclosporin, nicotinic acid, azole antifungals, protease inhibitors and macrolide antibiotics.
νώκιδοιρεπ νωτ αισίαλπ ςετηµύθιπενΑ
Gemfibrozil increases the risk of myopathy when given concomitantly with some HMG-CoA reductase inhibitors.
νεδ αίρυονϊετωρπ
Therefore, the combination of Crestor and gemfibrozil is not recommended.
Η ασυοπίελαιδ ή ήκιδοραπ νατή ςιεσώτπιρεπ ςερετόσσιρεπ ςιτσ υοπό
The benefit of further alterations in lipid levels by the combined use of
. ςιεσόδ ςερετόληψυ νυονάβµαλ υοπ ςίενεθσα εσ ίεθηρηταραπ ιεχέ ςησυελέορπ
10 Crestor with fibrates or niacin should be carefully weighed against the potential risks of such combinations.
ςήκαιρανηλωσ ςωίρυκ ιανίε υοπ ιακ
The 40 mg dose is contraindicated with concomitant use of a fibrate.
νώινιατ ησήρχ εµ ιατεύενχινα υοπ αίρυονϊετωρΠ (dipstick) ςύορφεν ςυοτσ ησαρδίπΕ
(See Section 4.5 Interaction with other medicinal products and other forms of interaction and Section 4.8 Undesirable effects.)
,
Crestor should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e. g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).
ησήρχ ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ ςέκιδιΕ
Liver Effects As with other HMG-CoA reductase inhibitors, Crestor should be used with caution in patients who consume excessive quantities of alcohol and/ or have a history of liver disease.
ιακ ςησαρδίπεληλλα ςέφροµ ςελλά ιακ ακαµράφ αλλά εµ 5. 2
It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment.
ησήρχ ητ άτακ ςιεξάλυφορπ ςερετίαιδι ιακ ςιεσήιοποδιεορπ ςέκιδιΕ
Crestor should be discontinued or the dose reduced if the level of serum transaminases is greater than 3 times the upper limit of normal.
νώταρβιφ ησηγήροχ ηνορχότυατ ςίενεθσα ςυοζένιΚ ιακ ςενωπάΙ
In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with Crestor.
αµσάλπ οτσ νωδέπιπε νωτ ησηξύα ίεθηρηταραπ αν ίεροπµ υοπό ςιεσάτσατακ λόοκλα ησηρχάτακ ςητάρβιφ ή
Race Pharmacokinetic studies show an increase in exposure in Japanese and Chinese subjects compared with Caucasians (see section 4.2 Posology and Method of administration and section 5.2 Pharmacokinetic properties)
ςησάγωγανα
4.5 Interaction with other medicinal products and other forms of interaction
12
Cyclosporin:
αν ίεροπµ ςιεσόδ ςερετόρκιµ εσ ησιµθύρ η ή
During concomitant treatment with Crestor and cyclosporin, rosuvastatin AUC values were on average 7 times higher than those observed in healthy volunteers (see Section 4.3 Contraindications).
υοτ ήποκαιδ Η
Concomitant administration did not affect plasma concentrations of cyclosporin.
(International Normalised Ratio).
Vitamin K antagonists:
INR ςέµιτ ςιτσ ησηξύα ιερέφιπε αν ίεροπµ ηνίραφραβ χ π Κ ςηνίµατιβ ςητ ςέτσινωγατνα ςωνόρχγυσ
As with other HMG-CoA reductase inhibitors, the initiation of treatment or dosage up-titration of Crestor in patients treated concomitantly with vitamin K antagonists (e. g. warfarin) may result in an increase in International Normalised Ratio (INR).
νυονάβµαλ υοπ ςίενεθσα εσ ςιεσόδ ςερετύλαγεµ εσ ησιµθύρ η ή
Discontinuation or down- titration of Crestor may result in a decrease in INR.
εµ ςαίεπαρεθ ςητ ηξρανέ
In such situations, appropriate monitoring of INR is desirable.
η ςησάγωγανα
Gemfibrozil and other lipid-lowering products:
ςητ ςίελοτσανα ςυολλά εµ ιακ ςωπΌ Κ ςηνίµατιβ ςητ ςέτσινωγατνΑ
Concomitant use of Crestor and gemfibrozil resulted in a 2-fold increase in rosuvastatin C max and AUC (see Section 4.4 Special warnings and special precautions for use).
αµσάλπ οτσ ςηνίροπσολκυκ ςητ αδεπίπε ατ εσαέρηπε νεδ ησηγήροχ ηνορχότυατ Η.
Based on data from specific interaction studies no pharmacokinetic relevant interaction with fenofibrate is expected, however a pharmacodynamic interaction may occur.
ραπ λβ ςέτνολεθε
These patients should also start with the 5 mg dose.
4. 3
Antacid:
εσ νακηθήρηταραπ υοπ ςέτυα εµ ησέχσ εσ ςερετόληψυ ςέροφ ορό οσέµ άτακ νατή ςητ ςέµιτ ιο ηνίροπσολκυκ ιακ AUC, εµ αίεπαρεθ ηνορχότυατ νητ άταΚ ηνίροπσολκυΚ
The clinical relevance of this interaction has not been studied.
7
11 Erythromycin:
rosuvastatin
Concomitant use of Crestor and erythromycin resulted in a 20% decrease in AUC (0-t) and a 30% decrease in Cmax of rosuvastatin.
εµ ςιεσάρδιπεληλλΑ ςετητόιδΙ ςέκιτηνικοκαµραΦ
This interaction may be caused by the increase in gut motility caused by erythromycin.
οφαργάραπ λβ ςυοισάκυαΚ ςυοτ
Oral contraceptive/ hormone replacement therapy (HRT):
Crestor, υοτ νώσανιµασναρτ νωτ ςιεσήξυα εΣ ςαίεπαρεθ ςητ ηξρανέ νητ άτεµ ςενήµ ςυοτσ ιακ ςαίεπαρεθ
Concomitant use of Crestor and an oral contraceptive resulted in an increase in ethinyl oestradiol and norgestrel AUC of 26% and 34%, respectively.
ςυολλά εµ ιακ ςωπΌ ραπή οτσ ςιεσάρδιπΕ
These increased plasma levels should be considered when selecting oral contraceptive doses.
ιακ ςέκιγολονιρκοδνε ςέκιλοβατεµ ςέραβοσ αµύαρτ ησαβµέπε ήκιγρυοριεχ νωζίεµ ησατόπυ ηψήσ
There are no pharmacokinetic data available in subjects taking concomitant Crestor and HRT and therefore a similar effect cannot be excluded.
ιενώληδοπυ υοπ ησατσάτακ ήραβοσ αίεξο εµ ήνεθσα νανένακ εσ ιατίεγηροχ αν ιεπέρπ εδ
However, the combination has been extensively used in women in clinical trials and was well tolerated.
ςειεγρένΕ ςετηµύθιπενΑ
Other medicinal products:
ςέφροµ ςελλά ιακ ατνόϊορπ άκιτυεκαµραφ αλλά εµ ςιεσάρδιπεληλλΑ
Based on data from specific interaction studies no clinically relevant interaction with digoxin is expected.
οφαργάραπ λβ
Cytochrome P450 enzymes:
ςητάρβιφ ησηγήροχ ηνορχότυατ εµ ιατυνκίεδνετνα
Results from in vitro and in vivo studies show that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes.
νωτ ησόδ ςύοτυα ςύοµσαυδνυσ ςυοτ όπα υονύδνικ υονεµόχεδνε υοτ ιτνανέ ήχοσορπ εµ ιατεζίµθατσ. H
In addition, rosuvastatin is a poor substrate for these isoenzymes.
αν ιεπέρπ ηνίσαιν ή ςετάρπµιφ εµ
No clinically relevant interactions have been observed between rosuvastatin and either fluconazole (an inhibitor of CYP2C9 and CYP3A4) or ketoconazole (an inhibitor of CYP2A6 and CYP3A4).
νωτ ήλοβατεµ ωρέτιαρεπ νητ όπα ςολεφό οΤ ιατάτσινυσ εδ ςηλίζορπµιφµεγ ιακ
Concomitant administration of itraconazole (an inhibitor of CYP3A4) and rosuvastatin resulted in a 28% increase in AUC of rosuvastatin.
ςητ ςίελοτσανα ςυοιοπάκ εµ όµσαυδνυσ εσ ιατίεγηροχ HMG- CoA
This small increase is not considered clinically significant.
, –, ςητ ςηνέµοναβµαλιρεπµυσ ςοέξο ύοκινι αγωγάραπ εµ ίζαµ ςησάγωγανα
Therefore, drug interactions resulting from cytochrome P450-mediated metabolism are not expected.
ςίελοτσανα
4.6 Pregnancy and lactation
ήγωγα ηλλά αιοπάκ εµ ςωνόρχγυσ
Crestor is contraindicated in pregnancy and lactation.
ςύοκιταµωτπµυσα εσ ςανίτυορ ησατέξε ςω,
Women of child bearing potential should use appropriate contraceptive measures.
νωδέπιπε νωτ ησηρτέΜ ησηθύολοκαραπ ήνετσ εµ ιακ CK,
Since cholesterol and other products of cholesterol biosynthesis are essential for the development of the foetus, the potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy.
ςητ αέλοτσανα ύοκιτκαλλανε ή
Animal studies provide limited evidence of reproductive toxicity (see Section 5.3 Preclinical safety data).
η ίεθσατεξε αν ίεροπµ ετότ ςέµιτ ςέκιγολοισυφ ςιτσ νυοσήρωχοπυ
If a patient becomes pregnant during use of this product, treatment should be discontinued immediately.
αδεπίπε ατ ιακ νυοθλέραπ
Rosuvastatin is excreted in the milk of rats.
αταµώτπµυσ ατ νάΕ
There are no data with respect to excretion in milk in humans.
ςησάνικ ςήκινιταερκ αδεπίπε ατ νύοθηρτεµ (CK).
(see Section 4.3 Contraindications).
αίεχιοτσ άκινιλκορΠ
4.7 Effects on ability to drive and use machines
5. 3.
Studies to determine the effect of Crestor on the ability to drive and use machines have not been conducted.
νυοχέραπ αωζόταµαριεπ εσ ςετέλεΜ ςαίεπαρεθ ςητ ςυολέφο υοτ ιεύχσιρεπυ ησηύκ νητ άτακ.
However, based on its pharmacodynamic properties, Crestor is unlikely to affect this ability.
ςητ ήλοτσανα νητ όπα ςονυδνίκ ςονεµόχεδνε ο υούρβµε υοτ ηξυτπάνα νητ
When driving vehicles or operating machines, it should be taken into account that dizziness may occur during treatment.
ςοταµώρχοτυκ
4.8 Undesirable effects
αίχυολαγ ιακ ησηύ P450.
The adverse events seen with Crestor are generally mild and transient.
ςητ ιακ
In controlled clinical trials, less than 4% of Crestor-treated patients were withdrawn due to adverse events.
υοτ ςαέλοτσανα ςηλόζανοκαρτι ησηγήροχ CYP3A4)
The frequencies of adverse events are ranked according to the following:
νωτ ςαέλοτσανα ςηλόζανοκοτεκ ςητ ή
Common (> 1/ 100 ,< 1/10); Uncommon (> 1/1 ,000, < 1/100); Rare (> 1/10,000, < 1/1000);
νωτ ςαέλοτσανα ςηλόζανοκυολφ ςητ ιακ
Immune system disorders Rare: hypersensitivity reactions including angioedema
ςητ ύξατεµ ςιεσάρδιπεληλλα ςέκιτναµησ rosuvastatin
Nervous system disorders Common: headache, dizziness
, η ιτό νυονχίεδ
12 Gastrointestinal disorders Common: constipation, nausea, abdominal pain
ηνίξογιδ εµ ςιεσάρδιπεληλλα ςέκιτναµησ άκινιλκ ιατνονέµανα νεδ.
Skin and subcutaneous tissue disorders Uncommon: pruritus, rash and urticaria
ανορχότυατ νυονάβµαλ υοπ αµοτά Crestor
Musculoskeletal, connective tissue and bone disorders Common: myalgia Rare: myopathy and rhabdomyolysis
αν ιεπέρπ αΘ αχιοτσίτνα.
General disorders Common: asthenia
άτακ ςηλέρτσεγρον ιακ ςηλόιδαρτσιολυνυθια ςητ 34% 26%
As with other HMG-CoA reductase inhibitors, the incidence of adverse drug reactions tends to be dose dependent.
νητσ
Renal Effects:
ησηξύα ερεφέπε όκιτπηλλυσιτνα ονεµύογηροχ ςοταµότσ υοτ όπα εµ
Proteinuria, detected by dipstick testing and mostly tubular in origin, has been observed in patients treated with Crestor.
νητσ ιατελίεφο αν ίεροπµ ήτυα ησαρδίπεληλλα Η ςητ άτακ ησωίεµ εσ εσηγήδο ηνίκυµορθυρε εµ
Shifts in urine protein from none or trace to ++ or more were seen in < 1% of patients at some time during treatment with 10 and 20 mg, and in approximately 3% of patients treated with 40 mg.
rosuvastatin
A minor increase in shift from none or trace to + was observed with the 20 mg dose.