Important Safety Information

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) used (off-label) in the treatment of premature ejaculation. Although it is NOT FDA-approved for the treatment of premature ejaculation, it is FDA-approved for the treatment of major depressive disorder (MDD), obsessive compulsive disorder (OCD), panic disorder (PD), social anxiety disorder (SAD), generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD).

Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor used (off-label) in the treatment of premature ejaculation. Although it is NOT FDA-approved for the treatment of premature ejaculation, it is FDA-approved for the treatment of erectile dysfunction and the signs and symptoms of benign prostatic hyperplasia (BPH).

IMPORTANT: This is a summary and does not have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

PAROXETINE CONTRAINDICATIONS:

• Concomitant use of monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing a MAOI.
• Concomitant use of pimozide or thioridazine.
• Known hypersensitivity to paroxetine.

PAROXETINE WARNINGS AND PRECAUTIONS:

• Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If occurs, discontinue paroxetine and initiate supportive measures.
• Embryofetal and Neonatal Toxicity: Can cause fetal and neonatal harm. Increased risk of cardiovascular malformations with exposure during the first trimester. Exposure in late pregnancy may lead to an increased risk for persistent pulmonary hypertension of the newborn.
• Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, other antiplatelet drugs, warfarin, and other anticoagulant drugs may increase risk.
• Activation of Mania/Hypomania: Screen patients for bipolar disorder.
• Seizures: Use with caution in patients with seizure disorders.
• Angle-Closure Glaucoma: Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
• Daily/Regular Use: Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible.

PAROXETINE SIDE EFFECTS:

Most common adverse reactions (≥5% and at least twice placebo) are abnormal ejaculation, asthenia, constipation, decreased appetite, diarrhea, dizziness, dry mouth, female genital disorder, impotence, infection, insomnia, libido decreased, male genital disorder, nausea, nervousness, somnolence, sweating, tremor, yawn. To report SUSPECTED ADVERSE REACTIONS, contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

PAROXETINE DRUG INTERACTIONS:

• Drugs Highly Bound to Plasma Protein: Monitor for adverse reactions and reduce dosage of paroxetine or other protein-bound drugs (e.g., warfarin) as warranted. • Drugs Metabolized by CYP2D6: Reduce dosage of drugs metabolized by CYP2D6 as warranted. • Concomitant use with tamoxifen: Consider use of an alternative antidepressant with little or no CYP2D6 inhibition.

PAROXETINE USE IN SPECIFIC POPULATIONS:

• Pregnancy: Can cause fetal and neonatal harm. Advise women of potential risk to the fetus. • Nursing Mothers: Discontinue drug or nursing, taking into consideration importance of drug to mother.

TADALAFIL CONTRAINDICATIONS:

• Administration of tadalafil to patients using any form of organic nitrate is contraindicated. Tadalafil was shown to potentiate the hypotensive effect of nitrate. • History of known serious hypersensitivity reaction (allergy) to tadalafil.

TADALAFIL WARNINGS AND PRECAUTIONS

• Patients should not use tadalafil if sex is inadvisable due to cardiovascular status.
• Use of tadalafil with alpha blockers, antihypertensives or substantial amounts of alcohol (≥5 units) may lead to hypotension.
• Tadalafil is not recommended in combination with alpha blockers for the treatment of BPH because efficacy of the combination has not been adequately studied and because of the risk of blood pressure lowering. Caution is advised when tadalafil is used as a treatment for ED in men taking alpha blockers.
• If taking potent inhibitors of CYP3A4, dose should be adjusted: tadalafil for use as needed: ≤10 mg every 72 hours. For once daily use: dose not to exceed 2.5 mg.
• Patients should seek emergency treatment if an erection lasts > 4 hours. Use tadalafil with caution in patients predisposed to priapism.
• Patients should stop tadalafil and seek medical care if a sudden loss of vision occurs in one or both eyes, which could be a sign of Non Arteritic Ischemic Optic Neuropathy (NAION). Discuss increased risk of NAION in patients with history of NAION.
• Patients should stop tadalafil and seek prompt medical attention in the event of sudden decrease or loss of hearing.
• Prior to initiating treatment with tadalafil for BPH, consideration should be given to other urological conditions that may cause similar symptoms.

TADALAFIL DRUG INTERACTIONS:

• Tadalafil can potentiate the hypotensive effects of nitrates, alpha blockers, antihypertensives or alcohol.
• • CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase tadalafil exposure. For concomitant use with potent CYP3A4 inhibitors, dose adjustment may be needed.
• CYP3A4 inducers (e.g. rifampin) decrease tadalafil exposure.

TADALAFIL USE IN SPECIFIC POPULATIONS:

Hepatic Impairment:
• Mild or Moderate: Dosage adjustment may be needed.
• Severe: Use is not recommended.
Renal Impairment:
• Patients with creatinine clearance 30 to 50 mL/min: Dosage adjustment may be needed.
• Patients with creatinine clearance less than 30 mL/min or on hemodialysis: For use as needed: Dose should not exceed 5 mg every 72 hours. Once daily use is not recommended.