Enclomiphene / Tadalafil Tablet

Patient Safety Information Sheet

IMPORTANT: This product is a compounded preparation containing enclomiphene citrate and tadalafil for oral use. The compounded combination is not approved by the U.S. Food and Drug Administration (FDA) and has not been evaluated by the FDA as a fixed-dose combination for safety, effectiveness, or quality. Enclomiphene is not an FDA-approved drug product. Tadalafil is FDA-approved in commercially available products for certain indications, but this compounded combination is not FDA-approved. This compounded medication is prescribed as part of an individualized treatment plan at the discretion of your healthcare provider.

What is Enclomiphene / Tadalafil Tablet?

Enclomiphene citrate is a selective estrogen receptor modulator (SERM) that has been studied in adult men with secondary hypogonadism. It acts primarily by reducing estrogen-mediated negative feedback at the hypothalamus and pituitary, which can increase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and stimulate the testes to produce endogenous testosterone.

Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor. It increases the effect of nitric oxide-mediated signaling in certain tissues and is used in FDA-approved products for erectile dysfunction and other approved indications. The presence of tadalafil in this compounded combination does not mean the combination itself is FDA-approved.

Your prescribing provider may recommend a compounded enclomiphene / tadalafil tablet as part of an individualized treatment plan. Enclomiphene is not FDA-approved, and the fixed-dose compounded combination has not been evaluated by the FDA for safety, effectiveness, or quality. Available enclomiphene clinical studies have not established long-term safety or demonstrated clinically meaningful improvement in all symptoms or signs of hypogonadism. Individual results vary, and no specific clinical outcome is guaranteed.

Active ingredients: Enclomiphene citrate and tadalafil
Route: Oral (taken by mouth)
Dosage form: Compounded Tablet
Strength: As stated on your pharmacy label

Who Should NOT Use Enclomiphene / Tadalafil Tablet

This medication is prescribed for adult men. Do not use this medication if any of the following applies to you:

• You have had an allergic or hypersensitivity reaction to enclomiphene, clomiphene, tadalafil, or any ingredient in the compounded tablet.
• You take any form of nitrate medication, such as nitroglycerin or isosorbide, or use recreational drugs containing nitrates (often called “poppers”). Combining nitrates with tadalafil can cause a dangerous drop in blood pressure.
• You take a guanylate cyclase (GC) stimulator such as Riociguat, because the combination with tadalafil may cause symptomatic hypotension.
• You have been advised that sexual activity is inadvisable because of your cardiovascular condition. Discuss this with your prescribing provider before using tadalafil-containing medication.
• You have active or a history of unexplained blood clots or a thromboembolic disorder unless your prescribing provider has specifically evaluated the risk and determined treatment is appropriate.
• You have uncontrolled or clinically significant liver disease unless your provider has specifically determined treatment is appropriate.
• If you are unsure whether any of these apply to you, talk to your prescribing provider or pharmacist before using this medication.

Warnings and Precautions

Blood clots and cardiovascular events. Serious thromboembolic and cardiovascular events, including deep vein thrombosis, pulmonary embolism, ischemic stroke, atrial flutter, bradycardia, and hypotension, were reported in enclomiphene clinical development. It is not known how much enclomiphene contributed to these events. Tadalafil can also lower blood pressure, and sexual activity may place additional strain on the heart in patients with cardiovascular disease. Seek urgent medical attention for chest pain, sudden shortness of breath, coughing up blood, one-sided leg swelling or pain, sudden weakness or numbness, severe dizziness, fainting, or new neurologic symptoms.

Hormone and laboratory changes. Enclomiphene may increase testosterone, LH, FSH, and estradiol. In clinical development, increases in hematocrit and prostate-specific antigen (PSA) were also reported. Your provider may order blood tests before and during treatment and may adjust or stop treatment based on the results.

Fertility and reproductive effects. Enclomiphene has been studied as a way to increase endogenous testosterone while maintaining sperm production in some men; however, fertility outcomes are not guaranteed. Discuss current or future fertility goals with your provider.

Low blood pressure and dizziness. Tadalafil may lower blood pressure. The risk can be greater with alpha-blockers, antihypertensive medicines, nitrates, GC stimulators, or substantial alcohol consumption. Tell your provider if you have low blood pressure, fainting, or dizziness. If you have chest pain after taking this medication, get emergency care and tell the care team you take tadalafil and when your last dose was.

Prolonged erection (priapism). Rarely, PDE5 inhibitors such as tadalafil can cause an erection lasting more than 4 hours. Seek emergency medical attention for an erection lasting more than 4 hours, whether painful or not, to reduce the risk of permanent injury.

Vision or neurologic symptoms. Selective estrogen receptor modulators (SERMs) can be associated with visual or neurologic symptoms. PDE5 inhibitors have also been associated rarely with sudden vision loss, including non-arteritic anterior ischemic optic neuropathy (NAION). Stop the medication and seek prompt medical attention for sudden loss of vision. Contact your provider promptly for new blurred vision, flashes, spots, severe headaches, or other significant visual or neurologic changes.

Hearing changes. Sudden decrease or loss of hearing, sometimes with ringing in the ears or dizziness, has been reported with PDE5 inhibitors. Stop the medication and seek prompt medical attention if this occurs.

Liver, kidney, prostate, and other medical conditions. Tell your provider if you have liver or kidney disease, active or suspected prostate cancer or elevated PSA, a history of blood clots, stroke, cardiovascular disease, abnormal hematocrit, significant low blood pressure, penile deformity, sickle cell disease, multiple myeloma, leukemia, or other significant medical conditions.

Do not exceed the prescribed dose. Higher doses or more frequent use may increase adverse effects, blood-pressure effects, hormone-related risks, and tadalafil exposure.

Possible Side Effects

Like all medications, enclomiphene and tadalafil can cause side effects. Because enclomiphene and this compounded fixed-dose combination are not FDA-approved, the complete safety profile and long-term risks of the combination are not fully established. Contact your provider or pharmacist for medical advice about side effects.

Possible side effects

• Headache
• Nausea, indigestion, or stomach discomfort
• Dizziness or flushing
• Back pain or muscle aches
• Nasal congestion
• Mood changes or irritability
• Changes in libido or energy
• Acne or oily skin
• Breast tenderness or enlargement
• Increased estradiol or other hormone changes
  

Less common or potentially serious side effects

• Blood clot in the leg or lung, stroke, or another thromboembolic event
• Abnormal heart rhythm, fainting, chest pain, or significant blood pressure changes
• Prolonged erection lasting more than 4 hours (priapism)
• Sudden decrease or loss of vision
• Sudden decrease or loss of hearing
• Increased hematocrit or red blood cell concentration
• Increased PSA or new/worsening urinary or prostate symptoms
• Significant visual changes or severe headache
• Serious allergic reaction: swelling of the face, lips, tongue, or throat; difficulty breathing; rash; or hives

Seek emergency medical care immediately for difficulty breathing, chest pain, coughing up blood, sudden weakness or numbness, one-sided leg swelling, fainting, an erection lasting more than 4 hours, sudden vision loss, or a serious allergic reaction.

Drug and Substance Interactions

Tell your provider and pharmacist about all prescription medications, over-the-counter medicines, vitamins, supplements, hormones, and substances you use. Formal drug-interaction data for enclomiphene is limited. Important considerations may include:

• Nitrates (including nitroglycerin and isosorbide) and recreational nitrate-containing products (“poppers”): do not use with tadalafil because of the risk of a dangerous drop in blood pressure.
• Guanylate cyclase stimulators such as riociguat: do not use with tadalafil because of the risk of symptomatic hypotension.
• Alpha-blockers and other blood-pressure-lowering medicines: combined use with tadalafil may increase dizziness, fainting, or low blood pressure. Your provider should determine whether the combination is appropriate.
• Substantial alcohol consumption may increase tadalafil-related blood pressure lowering, dizziness, headache, or fainting.
• Potent CYP3A4 inhibitors (for example, certain azole antifungals, HIV protease inhibitors, or other strong inhibitors) can increase tadalafil exposure. CYP3A4 inducers may reduce tadalafil exposure. Your provider or pharmacist should review your medication list.
• Other PDE5 inhibitors or erectile-dysfunction treatments should not be combined unless specifically directed by your prescribing provider.
• Testosterone, hCG, clomiphene, tamoxifen, aromatase inhibitors, or other medicines that alter sex-hormone signaling may substantially change testosterone, estradiol, LH, or FSH levels.
• Anticoagulants or antiplatelet medicines if you have bleeding or clotting concerns; your provider should review your overall thrombotic and bleeding risk.
• Medicines that affect liver enzymes or liver function, because enclomiphene pharmacokinetic and interaction data are limited.
• Other compounded or non-prescription hormone-support products may duplicate effects or make laboratory results harder to interpret.
• Do not start, stop, or change hormone-related medicines, erectile-dysfunction medicines, or supplements without discussing them with your prescribing provider.

Special Populations

Pregnancy. Enclomiphene has not been established as safe for use during pregnancy and this product is not intended for use in pregnant patients. If pregnancy is possible, discuss appropriate precautions with your provider before treatment.

Breastfeeding. Safety of this compounded combination during breastfeeding has not been established. Use is not recommended unless a qualified provider determines that the potential benefit justifies the potential risk.

Women. Enclomiphene has primarily been studied in adult men with secondary hypogonadism. Safety and effectiveness of this compounded combination for routine use in women have not been established.

Children and adolescents. Safety and effectiveness have not been established in patients under 18 years of age. This product is not intended for pediatric use unless specifically prescribed by a qualified provider.

Older adults. Clinical experience with enclomiphene is limited. Older adults may have a higher baseline risk of cardiovascular, thromboembolic, prostate, hematologic, renal, or blood-pressure complications and may require closer monitoring.

Liver or kidney impairment. Enclomiphene pharmacokinetic data and dose-adjustment guidance are limited, and tadalafil exposure may be affected by hepatic or renal impairment. Tell your provider if you have liver or kidney disease before starting treatment.

How to Use Enclomiphene / Tadalafil Tablet

Use this medication exactly as prescribed on your pharmacy label. The prescribed dose and schedule may vary based on your clinical history, laboratory values, treatment goals, other medications, and response.

Step-by-step use

• Take the tablet by mouth exactly as directed by your pharmacy label.
• Take doses at approximately the same time on scheduled treatment days unless your provider instructs otherwise.
• Do not take more than prescribed, use additional tadalafil/PDE5-inhibitor products, or take extra doses to make up for a missed dose unless specifically directed by your provider.
• Keep all recommended follow-up appointments and laboratory testing so your provider can assess testosterone, estradiol, LH/FSH, hematocrit, PSA when appropriate, blood pressure, treatment response, and other relevant parameters.
• Tell your provider if symptoms do not improve, worsen, or if you develop new adverse effects.

If you miss a dose
If you miss a dose, follow the instructions on your pharmacy label or contact your pharmacist or prescribing provider. Unless specifically instructed otherwise, do not double the next dose.

If you use too much
If you take more than prescribed, contact your provider or Poison Control at 1-800-222-1222. Seek emergency medical care for chest pain, difficulty breathing, fainting, severe neurologic symptoms, an erection lasting more than 4 hours, sudden vision loss, or a serious allergic reaction.

Storage and Disposal

• Store at controlled room temperature as directed on your pharmacy label, generally 20-25 degrees C (68-77 degrees F), unless your pharmacy instructs otherwise.
• Protect from moisture, excessive heat, and direct light.
• Keep the container tightly closed and store the medication in the original pharmacy-dispensed container.
• Do not store in a bathroom or other humid location.
• Do not use after the beyond-use date (BUD) printed on the pharmacy label.
• Do not use medication that is damaged, discolored, has an unusual odor, or appears different from when dispensed.
• Keep out of reach of children and pets.
• Dispose of unused or expired medication according to your pharmacist's instructions or through an authorized medication take-back program. Do not flush unless specifically instructed.

Reporting Side Effects

If you experience any side effects, contact your prescribing provider or the dispensing pharmacy - The Pharmacy Hub, 1-888-958-1382. Serious or unexpected side effects may also be reported to the FDA MedWatch program:

• Online: www.fda.gov/medwatch
• Phone: 1-800-FDA-1088 (1-800-332-1088)