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Patients with a history of NAION are at increased risk for recurrence.

Only use a PDE5 inhibitor in these individuals if the anticipated benefit outweighs the risk.

Patients with low cup to disc ratio ('crowded disc') are also at increased risk; however, this condition is uncommon, and there is insufficient evidence to support screening of prospective users of a PDE5 inhibitor.

Vardenafil use is not recommended in patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa.

A minority of patients with the inherited condition retinitis pigmentosa have genetic disorders of retinal phosphodiesterases.

Vardenafil use is not recommended in these patients until further information is available. There are no adequate and well-controlled trials of vardenafil in humans during pregnancy. In animal reproduction studies, no adverse developmental outcomes were observed during organogenesis at exposures for unbound vardenafil and its major metabolite at 100 and 29 times, respectively, the maximum recommended human dose (MRHD) of 20 mg. Vardenafil is not indicated for use in females and is therefore not recommended during breast-feeding. There is no information on the presence of vardenafil and its major metabolite in human milk, the effects on the

breast-fed

infant, or the effects on milk production. Vardenafil is excreted into the milk of lactating rats at concentrations approximately 10-fold greater than found in the plasma; following a single oral dose of 3 mg/kg, 3.3% of the administered dose was excreted into the milk within 24 hours.

There is no known indication for the use of vardenafil in neonates, infants, or children.

Vardenafil should not be prescribed to these populations.

Vardenafil should be used cautiously in patients with gastroesophageal reflux disease (GERD) or hiatal hernia associated with reflux esophagitis.

Like sildenafil, vardenafil can possibly decrease the tone of the lower esophageal sphincter and inhibit esophageal motility. Vardenafil should be administered to patients with coagulopathy only after careful benefit vs. Vardenafil alone does not prolong the bleeding time nor does its use in combination with aspirin cause any additive prolongation of the bleeding time. However, vardenafil has not been studied or administered to patients with bleeding disorders or significant active peptic ulcer disease.

Therefore administer to these patients after careful benefit-risk assessment.

Patients with a sudden decrease or loss of hearing (hearing impairment) should stop taking vardenafil and seek prompt medical attention. Hearing loss, which may be accompanied by tinnitus and dizziness, has been reported in temporal association with the intake of PDE5 inhibitors, including vardenafil; however, it is unknown if the hearing loss is directly

related

to PDE5 inhibitors or to other factors. The vardenafil orally disintegrating tablets contain aspartame, which is a source of phenylalanine.

This may be harmful for people with phenylketonuria. The vardenafil orally disintegrating tablets contain sorbitol. Patients with hereditary fructose intolerance should not take the orally disintegrating tablets.

anaphylactoid reactions / Rapid / 0-2.0 laryngeal edema / Rapid / 0-2.0 angioedema / Rapid / 0-2.0 seizures / Delayed / 0-2.0 ventricular tachycardia / Early / 0-2.0 myocardial infarction / Delayed / 0-2.0 visual impairment / Early / 0-2.teva 5343 white pill 0 hearing loss / Delayed / 0-2.0 non-arteritic anterior ischemic optic neuropathy / Delayed / Incidence not known.

erythema / Early / 0-2.0 amnesia / Delayed / 0-2.0 hypertonia / Delayed / 0-2.0 esophagitis / Delayed / 0-2.0 gastritis / Delayed / 0-2.0 dysphagia / Delayed / 0-2.0 angina / Early / 0-2.0 hypertension / Early / 0-2.0 sinus tachycardia / Rapid / 0-2.0 orthostatic hypotension / Delayed / 0-2.0 chest pain (unspecified) / Early / 0-2.0 hypotension / Rapid / 0-2.0 palpitations / Early / 0-2.0 dyspnea / Early / 0-2.0 ejaculation dysfunction / Delayed / 0-2.0 conjunctivitis / Delayed / 0-2.0 photophobia / Early / 0-2.0 blurred vision / Early / 0-2.0 hyperemia / Delayed / 0-2.0 elevated hepatic enzymes / Delayed / 0-2.0 priapism / Early / Incidence not known QT prolongation / Rapid / Incidence not known.

headache / Early / 14.4-15.0 flushing / Rapid / 7.6-11.0 rhinitis / Early / 9.0-9.0 dyspepsia / Early / 2.8-4.0 nasal congestion / Early / 3.1-3.1 sinusitis / Delayed / 3.0-3.0 dizziness / Early / 2.0-2.3 hyperhidrosis / Delayed / 0-2.0 photosensitivity / Delayed / 0-2.0 rash / Early / 0-2.0 pruritus / Rapid / 0-2.0 paresthesias / Delayed / 0-2.0 dysesthesia / Delayed / 0-2.0 asthenia / Delayed / 0-2.0 diarrhea / Early / 0-2.0 xerostomia / Early / 0-2.0 gastroesophageal reflux / Delayed / 0-2.0 nausea / Early / 2.0-2.0 abdominal pain / Early / 0-2.0 vomiting / Early / 2.0-2.0 muscle cramps / Delayed / 0-2.0 back pain / Delayed / 2.0-2.0 arthralgia / Delayed / 0-2.0 myalgia / Early / 0-2.0 vertigo / Early / 0-2.0 drowsiness / Early / 0-2.0 insomnia / Early / 0-2.0 syncope / Early / 0-2.0 pharyngitis / Delayed / 0-2.0 epistaxis / Delayed / 0-2.0 ocular pain / Early / 0-2.0 lacrimation / Early / 0-2.0 tinnitus / Delayed / 0-2.0. Abarelix: (Major) Concomitant administration of vardenafil and abarelix may cause additive QT prolongation and should be used together cautiously. Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly. Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients

receiving

phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly. Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly. Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly.

Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) The therapeutic effect of phenylephrine may be decreased in patients receiving phosphodiesterase inhibitors.

Monitor patients for decreased pressor effect if these agents are administered concomitantly. Alfuzosin: (Moderate) Due to the potential for symptomatic hypotension, patients

should

be stable on alfuzosin therapy before initiating therapy with the lowest starting dose of vardenafil.

Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of alfuzosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of vardenafil and alfuzosin.

Concurrent use of these medications may also increase the risk for QT prolongation.

Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.

Alfuzosin may prolong the QT interval in a dose-dependent manner. Alpha-blockers: (Moderate) Due to the potential for symptomatic hypotension, patients should be

stable

on alpha-blocker therapy before initiating therapy with the lowest dose of vardenafil. Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of the alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion.

Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of vardenafil and an alpha-blocker.

Amiodarone: (Major) The concomitant use of amiodarone and vardenafil should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone.

Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction)

The

effect of vardenafil on the QT interval should be considered when prescribing the drug. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP).

Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the

extremely

long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Amiodarone is an inhibitor of CYP3A4 and can reduce vardenafil clearance. Increased systemic exposure to vardenafil may result in an increase in vardenafil-induced adverse effects. Amoxicillin; Clarithromycin; Lansoprazole: (Major) The manufacturer of clarithromycin (a CYP3A4 inhibitor) recommends against concomitant use with vardenafil (a CYP3A4 substrate); as use of these drugs together will result in increased vardenafil exposure. If these drugs must be administered concurrently, use the regular tablet formulation of vardenafil at a dose not to exceed 2.5 mg every 24 hours. The vardenafil orally disintegrating tablets

provide

increased exposure as compared to the regular tablets; therefore, use of the orally disintegrating tablets with moderate or potent CYP3A4 inhibitors is not advised.

In addition, clarithromycin and vardenafil have been associated with prolongation of the QT interval; use of these drugs together may increase the risk for QT prolongation. Amoxicillin; Clarithromycin; Omeprazole: (Major) The manufacturer of clarithromycin (a CYP3A4 inhibitor) recommends against concomitant use with vardenafil (a CYP3A4 substrate); as use of these drugs together will result in increased vardenafil exposure. If these drugs must be administered concurrently, use the regular tablet formulation of vardenafil at a dose not to exceed 2.5 mg every 24 hours. The vardenafil orally disintegrating tablets provide increased exposure as compared to the regular tablets; therefore, use of the orally disintegrating tablets with moderate or potent CYP3A4 inhibitors is not advised. In addition, clarithromycin and vardenafil have been associated with prolongation of

the

QT interval; use of these drugs together may increase the risk for QT prolongation.

Amyl Nitrite: (Severe) Coadministration of phosphodiesterase inhibitors with organic nitrates or nitrites in any dosage formulation is contraindicated. Consistent with their known effects on the nitric oxide/cGMP pathway, concomitant use of phosphodiesterase inhibitors and nitrates can cause severe hypotension, syncope, or myocardial infarction.

Deaths have been reported in men who were using sildenafil while taking nitrate or nitrite therapy for angina. Anagrelide: (Major) Torsades de pointes (TdP) and

ventricular

tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary.

Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include vardenafil.

Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with vardenafil as concurrent use may increase the risk of QT prolongation.

Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines.

Vardenafil is also associated with QT prolongation at both therapeutic and supratherapeutic doses.

Aprepitant, Fosaprepitant: (Moderate) Use caution if vardenafil and aprepitant, fosaprepitant are used concurrently and monitor for an increase in vardenafil-related adverse effects for several days after administration of a multi-day aprepitant regimen. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of vardenafil. For example, a 5-day oral aprepitant regimen

increased

the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15)

increased

by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively.

As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively.

After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions.

However, as a single 150 mg intravenous dose, teva 5343 white pill fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Aripiprazole: (Moderate) Use caution when administering aripiprazole with vardenafil due to increased risk of QT prolongation. Vardenafil is associated with an increase in QTc interval at both therapeutic and supratherapeutic doses. QT prolongation has also occurred during therapeutic use of aripiprazole and following overdose. Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy.

QT prolongation should be expected with the administration of arsenic trioxide.

Torsade de pointes (TdP) and complete atrioventricular block have been reported.

Drugs

with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include vardenafil.

Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction).



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