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Concomitant Medications:
Consistent with vasodilatory effects of
alpha-blockers and vardenafil. the concomitant use of Vardenafil with alpha-blockers
may lead to symptomatic hypotension in some patients. Until further data are available,
a maximum dose of 5 mg Vardenafil with alpha-blockers must not be exceeded.
Vardenafil 5 mg should not be taken within 6 h of an alpha-blocker (see Interaction with
Other Medicaments and Other Forms of Interaction). Concomitant treatment should
only be initiated if the patient is stable on his alpha-blocker therapy.
A maximum dose of 5 mg should not be
exceeded when used in combination with the potent Cytochrome P450 (GYP) 3A4 inhibitor erythromycin.
A maximum dose of 5 mg should not be
exceeded when used in combination with the potent Cytochrome P450 (GYP) 3A4 inhibitors
ketoconazole and itraconazole. Vardenafil must not be taken with dosages of ketoconazole
and itraconazole higher than 200 mg. Concomitant use with HIV protease inhibitors such
as indinavir and ritonavir, which are very potent inhibitors of CYP3A4, is contraindicated.
Contraindications
Contraindicated in patients with
hypersensitivity to any of the drug's components (active or inactive ingredients).
Consistent with the effects of PDE
inhibition on the nitric oxide / cGMP - pathway, PDE5 inhibitors may potentiate the
hypotensive effects of nitrates. LEVITRAŽ is thus contraindicated in patients who
are concomitantly treated with nitrates or nitric oxide donors.
The safety of LEVITRAŽ has not been
studied in the following sub-groups of patients and its use is therefore contraindicated
until further information is available: severe hepatic impairment (Child-Pugh C),
endstage renal disease requiring dialysis, hypotension (resting systolic blood pressure
of < 90 mmHg), recent history of stroke or myocardial infarction (within last 6 months),
unstable angina, and known hereditary degenerative retinal disorders such as retinitis pigmentosa.
In men for whom sexual activity is not
recommended because of their underlying cardiovascular status, agents for
the treatment of erectile dysfunction should not be used.
Concomitant use of vardenafil with
potent CYP3A4 inhibitors such as ketoconazole and itraconazole (oral form) is
contraindicated in men older than 75 years. Concomitant use of Vardenafil with
HIV Protease inhibitors such as indinavir or ritonavir is contraindicated, as they are potent inhibitors of GYP 3A4.
Special warnings and special precautions for use
Prior to initiating any treatment for
erectile dysfunction, physicians should consider the cardiovascular status of their patients,
since there is a degree of cardiac risk associated with sexual activity.
Vardenafil has vasodilator properties which may result in mild and transient decreases in blood pressure.
Patients with left ventricular outflow obstruction, e.g., aortic stenosis and idiopathic
hypertrophic subaortic stenosis, can be sensitive to the action of vasodilators including Type 5 phosphodiesterase inhibitors.
A medical history and physical examination
should be undertaken to diagnose erectile dysfunction and determine potential
underlying causes, before pharmacological treatment is considered.
In a study of the effect of LEVITRAŽ on
QT interval in 59 healthy males, therapeutic (10 mg) and supratherapeutic (80 mg)
doses of LEVITRAŽ produced increases in QTc interval. This observation should be
considered in clinical decisions when prescribing LEVITRA. Patients with congenital
QT prolongation (long QT syndrome) and those taking Class IA (e.g., quinidine, procainamide)
or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications should avoid using LEVITRAŽ.
Agents for the treatment of erectile dysfunction
should generally be used with caution in patients with anatomical deformation of the penis
(such as angulation, cavernosal fibrosis or Peyronie's disease) or in patients who have
conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma or leukaemia).
Two cases of priapism were reported in
Phase I clinical study with 40 mg vardenafil (twice the maximum recommended dose).
In the event of an erection that persists longer than 4 hours, the patients should be
instructed to seek immediate medical assistance. If priapism is not treated immediately,
penile tissue damage and permanent loss of potency could result.
Vardenafil has not been studied in patients
with spinal cord injury or other CNS disease, hypoactive sexual desire and in patients
who have undergone pelvic surgery (except nerve-sparing prostatectomy), pelvic trauma
or radiotherapy. Therefore, the use of LEVITRAŽ in these patients is not recommended.
Levitra should be used with caution in patients with uncontrolled hypertension,
patients who have suffered life-threatening arrhythmias within the last 6 months and
patients with history of cardiac failure or coronary artery disease causing unstable angina.
The safety and efficacy of combinations
of LEVITRAŽ with other treatments for erectile dysfunction have not been studied.
Therefore the use of such combinations is not recommended.
Consistent with vasodilatory effects of alpha-blockers and vardenafil,
the concomitant use of Vardenafil with alpha-blockers may lead to symptomatic hypotension
in some patients. Until further data are available, a maximum dose of 5 mg Vardenafil
with alpha-blockers must not be exceeded. Vardenafil 5 mg should not be taken within
6 h of an alpha-blocker (see Interaction with Other Medicaments and Other Forms of Interaction).
Concomitant treatment should only be initiated if the patient is stable on his alpha-blocker therapy.
Concomitant use of the potent cytochrome P450 3A4 (CYP 3A4) inhibitors ketoconazole,
itraconazole, indinavir, or ritonavir can be expected to increase vardenafil AUC by 10-16 fold.
A maximum dose of 5 mg should not be exceeded when used in combination with erythromycin (increased vardenafil AUC by 4 fold).
A maximum dose of 5 mg should not be exceeded if used in combination with
ketoconazole and itraconazole. Vardenafil must not be taken with dosages of ketoconazole
and itraconazole higher than 200 mg (see Posology and Method of Administration).
Concomitant use with indinavir or ritonavir, which are highly potent inhibitors of CYP3A4, is contraindicated.
Grapefruit juice being a weak inhibitor of CYP3A4 gut wall metabolism,
may give rise to modest increases in plasma levels of vardenafil. The effects of the
concomitant use of vardenafil and grapefruit juice have not been studied, and should be avoided.
LEVITRAŽ has not been administered to patients with bleeding disorders or significant
active peptic ulceration. Therefore LEVITRAŽ should be given to these patients only after careful benefit-risk assessment.
In humans, Vardenafil has no effect on bleeding time alone or with acetylsalicyclic acid.
In vitro studies with human platelets indicate that Vardenafil alone did not
inhibit platelet aggregation induced by a variety of platelet agonists. With supertherapeutic
concentrations of Vardenafil a small concentration dependent enhancement of the
antiaggregatory effect of sodium nitroprusside, a nitric oxide donor, was observed.
The combination of heparin and Vardenafil had no effect on bleeding time in rats,
but this interaction has not been studied in humans.
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