How to decrease testosterone level in female

how to decrease testosterone level in female

Low Testosterone in Women

Low testosterone can cause side effects like decreased sex drive, depression and weakness in women and people assigned female at birth (AFAB). A blood test measures testosterone levels.

Overview

What is low testosterone in women?

Testosterone is a type of androgen hormone (or sex hormone) in your body. Hormones are chemical messengers that tell your body how to work and what to do. Everyone makes testosterone, but men and people assigned male at birth (AMAB) make the most testosterone. Women and people assigned female at birth (AFAB) also need testosterone, but at a much lower level.

Testosterone levels gradually begin to decrease as you enter your 30s. But you can experience low testosterone levels at any time in your life. Healthcare providers measure testosterone levels with a blood test.

Your ovaries, adrenal glands and other tissues and cells produce testosterone. Too little or too much testosterone can affect your overall health and impact the levels of other sex hormones in your body. The side effects of testosterone on women and people AFAB aren’t fully understood. Many treatment methods for low testosterone are unregulated and not widely studied. Only you and your healthcare provider can decide what’s best for you based on your symptoms and bloodwork.

How does testosterone affect a woman’s body?

Symptoms and Causes

What are the symptoms of low testosterone in women?

A blood test is the only way to know if your testosterone levels are low. However, there are some common signs of low testosterone to watch for, like:

  • Low sex drive (hypogonadism).
  • Lack of energy and feeling tired.
  • Loss of strength and muscle tone.
  • Infertility or trouble conceiving.
  • Irregular menstrual cycle.
  • Vaginal dryness.
  • Depression or anxiety.
  • Thinning hair.
  • Dry, brittle skin.
  • Trouble sleeping.

Talk to a healthcare provider if you struggle with any of these symptoms. They can evaluate you and assess if testosterone levels may be responsible.

What causes low testosterone in women?

Getting older (entering menopause) is one of the largest causes of low testosterone. By the time a person reaches menopause, their testosterone levels may have decreased by half of what they once were.

People who’ve had their ovaries removed (oophorectomy) will also have low testosterone levels because their ovaries are responsible for about half of all testosterone production.

Other than age and having your ovaries removed, other causes for low testosterone include:

  • Turner syndrome (a genetic condition where your ovaries don’t develop).
  • Tumor on your pituitary gland.
  • Chemotherapy.
  • Radiation.
  • Ovarian insufficiency.
  • Adrenal insufficiency (Addison’s disease).
  • Malnutrition (like from anorexia or extreme malnourishment).
  • Hyperprolactinemia (too much of the hormone prolactin).
  • Hypothalamic amenorrhea (loss of your menstrual period from extreme stress, weight loss or exercise).
  • Premature menopause (menopause before 40 years old).

Medications that can lower testosterone levels include:

Some people may also have something in their genetic makeup (their DNA) that interferes with their body’s ability to produce or process DHEA and DHEA-S. These are two compounds that convert to testosterone.

Diagnosis and Tests

How is low testosterone diagnosed?

First, your healthcare provider does a physical examination and talks to you about your symptoms and medical history. They may order blood work to check hormone levels. Many providers hesitate to diagnose low testosterone because research on the link between testosterone levels and specific symptoms isn’t well known. Low testosterone is often hard to diagnose because its symptoms mimic other conditions like depression, thyroid issues or low iron (anemia).

Measuring testosterone levels involves a blood test. Your blood test results can vary depending on when the test is taken. This is because hormone levels fluctuate throughout your menstrual cycle and even between morning and evening. If you’re still getting a period, there’s a specific window in your cycle that’s best for measuring testosterone in your blood.

What should a woman’s testosterone level be?

It depends on your age. Testosterone levels decline with age throughout a person’s life, starting in their 30s. For example, low testosterone in a 30-year-old is a different value than low testosterone in a 50-year-old. Healthcare providers don’t have a standard value for “normal” testosterone levels in women and people AFAB.

Management and Treatment

How is low testosterone treated?

Treatment for low testosterone can be controversial because low testosterone in women and people AFAB hasn’t been well-studied. The U.S. Food and Drug Administration (FDA) hasn’t approved any testosterone treatments currently. As there isn’t a standard for treatment, providers treat low testosterone in women the same way they’d treat it in men. This can be problematic because women and people AFAB require significantly less testosterone (a much lower dose of medication) than men and people AMAB.

Testosterone can come in many forms, like:

Taking DHEA pills can also be an option. As DHEA is a precursor to testosterone, taking a supplement may help your body create testosterone. DHEA is available without a prescription but isn’t regulated by the FDA.

You should discuss the risks of each treatment method with your healthcare provider before deciding. Many well-respected medical societies and healthcare experts advise against treating low testosterone in women unless specific criteria are met.

What are the risks of hormone therapy for low testosterone?

If you decide to take testosterone supplements, you’ll need close monitoring for side effects. Some of these are:

Viagra online

viagra online

Viagra.
Viagra (sildenafil) tablets to treat erectile dysfunction available to buy online in 25mg, 50mg, and 100mg strengths.
Buy Viagra online in UK.
Order Viagra from our online pharmacy for UK delivery:
Read medical information about erectile dysfunction Answer medical questions to check for eligibility Reviewed by doctors – medication posted from UK pharmacy (tracked 24hr service)
Men should have an erectile dysfunction diagnosis from a GP before obtaining medication online.
Generic Viagra also available.
Lower cost generic Viagra, called sildenafil, has been available since Viagra’s patent expired in the UK in June 2013. Sildenafil citrate is the medical name of the active ingredient in Viagra. Sildenafil is much cheaper from 71p per tablet – branded Viagra cost £5. They contain the same medicine.
Prices.
Viagra cost (in stock) Tablet type 4 tablets 8 tablets 16 tablets 32 tablets 64 tablets Sildenafil 25mg £4.90 £8.50 £15.20 £29.50 £45.50 Sildenafil 50mg £6.50 £11.90 £23.00 £44.00 £60.95 Sildenafil 100mg £7.20 £13.25 £26.00 £49.00 Viagra 25mg £24.20 £44.30 £82.00 n/a n/a Viagra 50mg £29.40 £59.50 £112.60 n/a n/a Viagra 100mg £33.80 £64.45 £124.50 n/a n/a.
Price match guarantee Prescription issued online – small prescription fee per order.
Compare prices: Dr Fox pharmacy prices are 25%-50% lower cost than other online pharmacies.
Prescription fees.
Dr Fox supplies medicine on prescription and charges a small prescription fee based on the order value of each prescription.
Prescriptions are issued by our doctors online and sent electronically to our pharmacy.
Dr Fox prices are 25%–50% lower than other UK online clinics.
The prices shown are listed by the online clinics named after a customer first enters consultation information and is offered prescriptions. It is possible these clinics may have special offers or lower prices for repeat supplies. Prices may change and are, to the best of our knowledge, accurate on the date stated. All products in stock and new condition. Dr Fox does NOT claim to provide a superior service to any of the online clinics listed. All the clinics listed, as far as we can tell, comply with all regulation and, as far as we can tell, operate to high ethical standards. Dr Fox adds a small prescription fee not included in the table (between £1 and £4 depending on value of the order). To amend the information in this table please contact us The prices listed in the table do not identify the cost of prescription medicine as online clinics charge a single fee to cover services which includes advice, consultations, prescriptions, and dispensing and supply of treatments. Where services include free delivery this is using the slowest delivery option available. Dr Fox uses Royal Mail Tracked 24.
Delivery charges.
UK delivery only: £2.90 per consultation via Royal Mail 24 Signed For (1-3 working days with tracking).
About Viagra.
Viagra is a prescription-only medicine used to treat erectile dysfunction ( ED ) in men. ‘Viagra’ is a brand name, the active ingredient is ‘sildenafil’. Starting dose is one 50mg tablet in 24 hours. Depending on results, adjust to 25mg or 100mg. Take 30-60 minutes before sexual activity, usually lasts for 4 hours. Sexual stimulation is required for Viagra to be effective. Read the patient leaflet for a full list of side effects, cautions, and interactions with other drugs. Large meals, fatty food, alcohol, and grapefruit can affect efficacy. Patent expired 2013 in the UK – cheaper generic sildenafil available.
How does Viagra work?
Viagra works by increasing blood flow to the penis when sexually stimulated, which helps men get and sustain an erection long enough for sex.
How to take.
The usual first starting dose of Viagra is one 50mg tablet, for men who have not used it before, although men over the age of 65 years would normally start on the lowest dose tablet (25mg).
Viagra works 30 to 60 minutes after it is taken and usually remains active for 4 hours.
If 50mg strength of tablet is highly effective subsequent doses may be reduced down to one 25mg tablet. If a 50mg tablet is ineffective, or the duration of activity is less than 4 hours, the dose can be increased to one 100mg tablet. Do not take Viagra more than once per day, or more than 100mg dose.
Arousal is required for the treatment to work. Viagra is most likely to be suitable if taken in situations where sexual arousal is expected within an hour or two of taking the tablet. Without sexual arousal there will be no benefit and the effect of the tablet will simply wear off after about 4 hours.
Avoid large meals, meals high in fat, excessive alcohol, and grapefruit as these can affect efficacy (effectiveness).
Dosage.
Viagra 25mg.
Reduced dose recommended when 50mg starting dose is highly effective.
Viagra 50mg.
Starting dose usually recommended for most men taking Viagra for the first time.
Viagra 100mg.
Strongest dose pill for when 50mg is ineffective.
Do not take more than 1 dose or more than 100mg in 24 hours, or combine with other erectile dysfunction drugs.
Does it work every time?
Satisfactory erections require the following:
If erectile dysfunction is the result of spinal injury or operation, nerves might be damaged. In this case Viagra may help a little but other measures, such as injections or stiffening aids, may be required.
Other causes of erectile dysfunction may require specialist treatment apart from tablets. Some men, whose erectile dysfunction has psychological causes, may benefit from counselling.
Viagra (sildenafil) dosage Men reporting improved erections 25mg 62% 50mg 74% 100mg 82%
Are there any side effects?
Viagra is remarkably well tolerated and free from significant side effects in the vast majority of men who take it. Viagra increases blood flow which can have adverse effects on other parts of the body, although these are usually mild. Most men who experience side effects carry on treatment regardless.
Slightly over 1% of men taking Viagra notice a bluish or yellowish discolouration of their vision. This is not in itself a cause for concern, and usually does not interfere with normal activity. It wears off after a few hours.
The most commonly reported adverse reactions in clinical studies were:
Headache – very common and can be treated with simple painkillers such as paracetamol. Flushing (redness of the skin, typically over the cheeks or neck). Indigestion (dyspepsia) – can be treated with indigestion remedies. Visual disorders/distortion . Nasal congestion – can be treated with menthol or eucalyptus inhalers. Dizziness – if affected it is recommended not to drive or operate machinery.
In the rare event of serious side effects seek immediate medical advice. This applies particularly to chest pains (possibly heart attack), loss of vision, and a prolonged and painful erection.
Priapism is the medical name for prolonged painful erections which have the potential to cause permanent damage to the penis. Priapism is rare. A persistent and painful erection of more than 2 hours requires immediate emergency medical attention.
Warnings.
Men with the following conditions should not take Viagra without further assessment from their GP :
Taking medicines called nitrates (often given for chest pain) Taking or intend to take amyl nitrite (‘poppers’) Taking riociguat (to treat high blood pressure in the lungs) Low or high blood pressure Allergies or reactions to past ED treatments Recent heart attack (within 6 weeks) or suffer from angina (heart pain on exertion) or any form of heart disease History of strokes or mini-strokes (transient ischaemic attack) History of vision problems caused by circulation problems History in the family of rare degenerative eye disease Serious kidney (renal) or liver disease Peyronie’s disease – angulation or deformity of the penis Leukaemia, multiple myeloma or sickle cell disease Bleeding disorders (such as haemophilia) Current active stomach ulcers (peptic ulcer or gastric ulcer) Lactose intolerant (tablets contain lactose)
Dr Fox cannot supply ED treatment to men who have any of the above conditions.
Recreational misuse.
Viagra is sometimes used for recreational rather than therapeutic purposes. If taken in this way, particularly in combination with non-prescribed drugs, there is an increased risk of significant side effects, some of which may be serious.
Patient Information Leaflet.
The Patient Information Leaflet ( PIL ) is the leaflet included in the pack with a medicine and must be read before taking the medicine. It is written for patients and gives information about taking or using a medicine.
Viagra Connect.
Viagra – the little blue pill recognised across the world – changed the face of erectile dysfunction treatment when it was launched by Pfizer in 1998. With its relatively few side effects, ease of use and proven effectiveness, it is little wonder the drug has become so popular.
In November 2017 the UK s medicines regulator, the MHRA , approved an application by Pfizer to reclassify its sildenafil 50mg to a ‘P’ medicine (available over the counter without a prescription) which is sold as a new product called Viagra Connect.
Alternative treatment.
Other oral ED drugs work in a similar way, with similar side effects. Viagra was the first drug in this class to become widely prescribed.
Sildenafil (generic Viagra) Cialis (tadalafil) Tadalafil (generic Cialis) Levitra (vardenafil) Vardenafil (generic Levitra) Spedra (avanafil)
Other treatments for ED include topical applications, injections into the penis, surgical devices, penis pumps, and counselling.
Why do men get erectile dysfunction?
Many factors can contribute to erectile dysfunction (also known as impotence). Lifestyle choices, such as excessive drinking, smoking, illegal drug use, as well as obesity and stress, can all have an impact on erections. Erectile dysfunction can also be a symptom of underlying health problems such as atherosclerosis (narrowing of the arteries), heart disease, and diabetes, amongst others.
Men suffering from erectile dysfunction should inform their GP s who will undertake an assessment, possibly perform tests, and provide advice. GP s are trained to deal with ED and are sympathetic to any embarrassment it may cause.
Further reading.
Viagra FAQs.
Do Viagra tablets become less effective over time?
Not usually. Studies show men usually find the same dose will be effective over a period of years. The body does not get used to the medicine. ED tends to be a slowly progressive condition, increasing with age, however unless there is an underlying medical progression the same dose should produce the same effect.
What is the difference between Viagra and sildenafil?
What is the difference between Viagra, Cialis, and Levitra?
The main difference is their duration of action: Viagra (sildenafil) works for about 4 hours; Levitra (vardenafil) for 4-5 hours; and Cialis (tadalafil) for about 36 hours. Each of these medicines work in the same way, by changing the blood flow in the penis, and side effects are similar. Some men find one works better for them than another, although most men find each one equally effective, but for different durations. Men can choose which tablet they use depending on the time they expect to be sexually active. An erection will only occur in the presence of arousal, and without it the treatment remains inactive.
Can I get Viagra on the NHS ?
Can my regular doctor give me a private prescription for Viagra?
Can I split tablets?
Viagra tablets are scored and can be broken in two. This may be a more cost effective way of using the treatment as the cost of the tablets is not proportional to the amount of active ingredient. A 100mg tablet does not usually cost twice as much as a 50mg tablet. If you find a 50mg tablet is effective, then half a 100mg will be just as good, as will two 25mg tablets. It is the overall amount of active ingredient which matters. 25mg tablets (the lowest dose available) should not be cut in half. The remaining half-tablet should be wrapped in eg clingfilm to prevent it drying out, if not used within a few days.
Dividing tablets is common practice – it is recommended to use a pill cutter for optimum results.
Can ED oral treatments be combined?
No. The commonly used ED oral treatments all work in the same way. Using more than one at the same time will not make treatment more effective, and risks overdose and unwanted side effects. Leave a gap between using one type of treatment and another of at least 24 hours.
Why shouldn’t I drink alcohol when taking Viagra?
It is recommended not to drink alcohol or only a minimal amount of no more than one or two units. Alcohol increases symptoms of erectile dysfunction. There is no direct chemical interaction between sildenafil and alcohol, however the risk of side effects such as a drop in blood pressure and even fainting will increase when used after heavy drinking. The treatment may also be less effective.
Why should men with ED consult their regular doctors before using ED treatment?
ED can be a sign of an underlying medical condition, such as reduced circulation, diabetes, high cholesterol, or a neurological or hormonal issue. These things need to be assessed by a doctor face-to-face, which may include tests, and men taking ED tablets should have check-ups periodically. It is safe to obtain Viagra online from UK regulated pharmacies, however proper diagnosis and review are required.
Can stress cause ED ?
Yes, particularly stress in a relationship or around sexual activity can cause erections to fail. Erections are usually stronger in men who are relaxed, rested, and comfortable with their partners. Counselling can be effective for some men who have ED , particularly younger men who have no underlying physical cause of their ED .
What are the risks of taking Viagra with recreation or illegal drugs?
Men taking ED tablets and drugs at the same time are open to numerous risks, from impulsive unsafe behaviour, excessive dosing, and increased side effects, to the serious and potentially irreversible damage caused by the rare condition of priapism. Priapism is a painful erection lasting more than 2 hours which can cause permanent damage to your penis if not treated quickly. There is an increased risk of priapism when Viagra is taken with cocaine.
ED tablets should not be taken with amyl nitrate (‘poppers’) as the combination can lead to a dangerous fall in blood pressure.
Why does the cost of ED treatment vary so much?
Pharmacies providing medicine on private prescriptions are free to charge what they choose. Some pharmacies will charge higher prices and make bigger profits, others may choose cheaper prices in the expectation that men will return when buying repeat supplies.
Is Viagra still prescription only medicine?
Are Viagra, Cialis, and Levitra as strong as each other?
Yes, generally men will respond equally well to the equivalent dose of these tablets. The equivalent strengths of each is as follows:
Drug Low strength Medium strength High strength Viagra (sildenafil) 25mg 50mg 100mg Cialis (tadalafil) 5mg 10mg 20mg Levitra (vardenafil) 5mg 10mg 20mg.
Some men might find they feel a stronger response to one type of treatment rather than another although this is generally not the case. There is also an alternative daily dose of Cialis 2.5mg and 5mg tablets for men who require continuous treatment.
Should I take Viagra on an empty stomach?
Viagra tablets will usually take around 30-45 minutes to take effect when taken on an empty stomach, and up to 60-90 minutes if taken within 30 minutes after a meal. High-fat meals will delay absorption longer than lower-fat ones.
Can Viagra go out of date?
The shelf life of most medicine tablets is 5 years. This means they will stay in-date for 5 years after the manufactured date written on the packet. It should be stored at below 30°C, which means keeping tablets out of direct sunlight. Packets will be printed with expiry dates and you should always read the information leaflet enclosed in packs.
Tablets remain effective after their ‘use-by’ date expires – see medicine expiry dates – however official advice is they should be taken to a pharmacy for safe disposal.
Authored 7 December 2012 by Dr Tony Steele MB ChB Sheffield University 1983. Former hospital doctor and GP .
Reviewed by Dr C. Pugh, Dr B. Babor, Dr A. Wood, Dr P. Hunt Last reviewed 18 August 2021 Last updated 1 June 2023.
References.
Pfizer, 2020, Viagra: Summary of Product Characteristics, accessed 18 August 2021 Pfizer, 2014, FDA : Label: VIAGRA (sildenafil citrate) tablets, accessed 18 August 2021 BNF / NICE , 2017, SILDENAFIL, accessed 18 August 2021.

How long does 20mg of cialis stay in your system

how long does 20mg of cialis stay in your system

How Long Does Cialis Stay in Your System?
Cialis (tadalafil) is the third prescription drug approved by the US FDA for treating erectile dysfunction (ED) or impotence in men. Clinically, the term impotence is no longer being used and the inability of a man to get and keep an erection firm enough for sexual intercourse is simply referred to as male erectile disorder or erectile dysfunction. In lay usage, impotence has a derogatory connotation and its true meaning often confused many. Impotence is a reproductive system disease in which one is unable to engage in a sexual act due to various reasons, which may include sexual arousal problems, premature ejaculation, inability to gain an erection, or having a weak erection. In this sense, the term can also be applied to women sexual disorders.
Cialis, just like Viagra (sildenafil) and Levitra (vardenafil), is a reversible phosphodiesterase 5 inhibitor (PDE5) that enhances erectile response to sexual stimulation by increasing blood flow to the penis. Compared to sildenafil and vardenafil, tadalafil has the longest duration of action. Cialis stays in your system for up to 36 hours or more, though there are other factors that can affect how long the drug stays in your body. The half-life of Cialis is 17.5 hours, while Viagra has a half-life of 3–5 hours. That is why the effects of Cialis can last for up to 2 days or more. As with all medications, Cialis can affect each person differently.
Treatment approaches for Cialis.
The major selling point of the branded tadalafil is its long-lasting action. The drug should be taken 30 minutes prior to sexual activity, and its average onset of action is 16–45 minutes. You can take Cialis with or without food, but many individuals reported early onset of action when it’s taken on an empty stomach. While other PDE5 inhibitors are taken on an as-needed basis, Cialis can also be taken on a daily basis, but in a lower dose. The usually prescribed dosage is 10mg as needed, and 2.5–5mg for daily usage. As a daily regimen, you should take Cialis around the same time each day for best results.
Safety and tolerability.
Concomitant use of nitrates, including recreational inhalation drug known as poppers, with PDE5 inhibitors is contraindicated. When coadminstered with antihypertensive drugs, tadalafil lowers blood pressure at 4 to 10mm Hg. If you are taking antibiotics or antifungal drugs, limit dosage to 10mg within a 72-hour period. In contrast with Viagra, changes in color vision is reported less in Cialis (less than 0.1 percent). Tadalafil does not inhibit PDE6, which may account for fewer reported visual disturbances. Tadalafil also inhibits PDE11, which is expressed in the prostate, liver, kidney, and skeletal muscles, more than sildenafil but its effects are unknown. The most common side effects associated with tadalafil are:
There are rare reports of priapism (persistent and painful erection of the penis lasting for several hours) in all medications in this drug class. Priapism is a medical emergency that can cause permanent damage to your penis if not treated immediately. You can employ some strategies to reduce erection as long as they do not delay timely medical attention:
You may exercise by climbing stairs or going for a walk; Take pain relievers such as paracetamol if needed; Hydrate by drinking lots of water; Have a warm bath or take a shower; Try to pee; Ice pack may relieve symptoms for ischemic priapism; Do not masturbate; Do not smoke or drink alcohol.
In a multicenter, open-label trial spanning 12 months and involving 1,173 patients, tadalafil was safe and well tolerated. 74.8% of patients, with mean age of 57, were taking concomitant medications for controlling comorbid conditions, such as diabetes mellitus and high blood pressure. There were four non tadalafil-related deaths that occurred during the trial. The study demonstrated that tadalafil at doses of 5, 10, and 20mg taken as need for 18–24 months was safe and well tolerated, supporting the long-term use of the drug for the clinical management of ED.
Potency.
In five clinical trials comparing tadalafil with placebo, 68 to 77% out of 321 men reported an erection suitable for insertion, compared with 42 to 55% in the placebo group. However, only 50 to 70% reported successful intercourse. Participants’ satisfaction with intercourse was reported at 9.3 and 7.4 in the placebo group out of a maximum score of 15. Overall satisfaction was 6.7 over 10.

When to take cialis 5mg

when to take cialis 5mg

Cialis® 5mg.
Cialis® contains the active ingredient, Tadalafil. Tadalafil is used to treat erectile dysfunction, a condition where you are unable to get or keep an erection firm enough to have sexual intercourse. It works by relaxing the blood vessels in your penis, allowing blood to flow into your penis when you get sexually excited. It can also be used for urinary symptoms associated with benign prostatic hyperplasia (enlarged prostate) with or without erectile dysfunction at the same time. It improves blood flow to, and relaxes the muscles of the prostate and bladder which may reduce symptoms of benign prostatic hyperplasia. For this indication, it has to be taken on a daily basis.
Dosage and how to use.
Take on a daily basis. Take at approximately the same time daily without regard to timing of sexual activity. This medication may be taken with or without food. Swallow the tablet whole. Do not split, crush or chew the tablet. Do not take more than the dose prescribed to you.
When do I take Cialis® 5mg vs Cialis® 20mg?
How often do you have sex? If it’s two or more times a week, a daily pill might be a reasonable choice, since the drug continually circulates in your bloodstream. How important is spontaneity? A daily pill clears the path for sex at any time, any day. On the other hand, the 36-hour window offered by the non-daily version of Cialis might offer enough spontaneity. Have side effects of your current ED pill been bothering you? Taking a daily low-dose pill may reduce side effects, though it may reduce effectiveness as well.
How effective is Tadalafil for Erectile Dysfunction?
Tadalafil has been shown to be highly effective in ED treatment. 3 studies with a total of over 1000 patients demonstrated significant improvement in erectile function and the ability to have successful sexual intercourse up to 36 hours following Tadalafil dosing.
The effects of Tadalafil last noticeably longer than that of Sildenafil (Viagra), normally up to 36 hours. This, however, does not mean you will have an erection for a day and a half. Instead, you will be able to achieve an erection within that 36-hour period.
What to do if I missed a tablet?
Take the missed dose as soon as you remember. If it is close to the time for your next dose, skip the missed dose and go back to your normal time. Do not take 2 doses at the same time or extra doses. Do not take more than the dose prescribed to you.
What are the possible side effects of Tadalafil?​
Facial flushing where the skin on your face feels hot Headache Nausea Back pain, muscle aches, pain in arms and legs Nasal congestion Very rarely, priapism (an erection that will not go away) – If you have an erection that lasts more than 4 hours, get medical help right away. If it is not treated right away, priapism can permanently damage your penis.
What precautions should I take?
Inform your healthcare professional if:
You are allergic to this medication or any of the other ingredients of this medication You are taking medicines called Nitrates (such as sublingual nitroglycerin (also known as Glycerin Trinitrate or GTN), Isosorbide Mononitrate or Isosorbide Dinitrate), as the combination may lead to a dangerous fall in your blood pressure. Nitrates must be withheld at least 24 hours after the last dose of Sildenafil or Vardenafil, and 48 hours after the last dose of Tadalafil. Tell your doctor if you are taking any of these medicines which are often given for relief of angina (chest pain). If you are not certain, ask your healthcare professional. You are taking medicines called Alpha-1 Blockers (such as Tamsulosin, Terazosin, Prazosin, Alfuzosin), as the combination may further lower your blood pressure. In order to reduce the chances of these symptoms occurring, you should be on a regular daily dose of your Alpha-blocker before you start drugs for erectile dysfunction. You recently had a stroke or a heart attack, low blood pressure or uncontrolled high blood pressure You have severe heart, liver or kidney problem You have certain rare inherited eye diseases (such as retinitis pigmentosa) You have a stomach ulcer or bleeding problem You have a deformity of your penis.
What other medications and foods should I avoid when taking Cialis®?
Avoid taking grapefruit, or grapefruit juice as they may interact with your medication and increase the risk of side-effects.
Drinking alcohol can temporarily weaken your ability to get an erection and may increase the blood pressure lowering effects of the medication, which can be dangerous. To get the maximum benefit from your medication, it is advisable not to drink excessive amounts of alcohol before taking this medication.
Inform your healthcare professional if you are taking or intend to take any other medication, supplements, traditional medications or herbal remedies.
This includes certain medications such as:
Antibiotics Anti-fungal medications Medications used to treat human immunodeficiency virus (HIV) infection Medications for epilepsy (fits)
Handling and storage.
Store in a cool and dry place, away from direct sunlight. Keep this medication away from children. Pack this medication into a black trash bag and seal it tightly before throwing into the rubbish chute or bin.
If you take more than the recommended dose, please seek medical advice immediately. The information provided on this page does not replace information from your healthcare professional. Please consult your healthcare professional for more information.

5mg cialis not working

5mg cialis not working

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Cialis generic

cialis generic

Top Tadalafil (Generic Cialis) FAQs answered.
Cialis is a popular and effective erectile dysfunction (ED) medicine that was first approved by the U.S. Food and Drug Administration in 2003. Since that time, Cialis has grown in popularity, coming to rival the best-known ED tablet on the market, Viagra.
When the patent on Cialis ran out in the UK in November 2017, pharmaceutical manufacturers were able to bring the cheaper generic version of Cialis, a medicine called Tadalafil, to UK patients.
The term ‘generic’ is applied to medicines which have not been produced by the original pharmaceutical company that manufactured them. Generic medicines are not branded and can only be manufactured after the patent on the original medicine has expired. This happened with the erectile dysfunction tablet Viagra – when its patent expired in 2013, the generic medicine Sildenafil, became available.
Generic Cialis is labelled Tadalafil because the active ingredient (the chemical that treats erectile dysfunction) is called tadalfil. In the same way, you might buy a tablet labelled ‘paracetamol’ rather than a branded pain medication.
Generic Cialis, or Tadalafil, is the same as Cialis in terms of its active ingredient (tadalafil), its effectiveness and side effects. The difference you may see is in the cost, with generic medicines tending to be less expensive.
We answer your top Tadalafil questions.
Following the UK launch of Tadalafil, many new questions have arisen… Keep reading for the low-down on Tadalafil and the answers to your frequently asked questions.
Tadalafil vs Cialis – Is there a difference?
From a medical perspective, both Cialis and Tadalafil work in the same way. From a medical perspective, both Cialis and Tadalafil work in the same way. Tadalafil is the active drug in both medications. The contrast all comes down to branding, marketing and distribution. An example of a similar situation is Viagra and Sildenafil. Both ED treatments work in the same way, and the active ingredient of Viagra is Sildenafil. However, due to branding, marketing and promotional strategies, Viagra is often favoured among the two.
Tadalafil vs Viagra – is Tadalafil better?
Both Tadalafil (generic Cialis) and Viagra are effective treatments for erectile dysfunction, but they do differ in some ways. Although the time to take effect is the same for both Tadalafil and Viagra (30-60) minutes, the length of time these ED treatments will remain effective vary. Overall, which one to choose is down to individual preference and suitability.
How long does Tadalafil last?
With Viagra, men can expect to gain erection within a 4-6-hour timeframe, whereas the effect of Tadalafil can last for up to 36 hours. This difference means that with Tadalafil you could reach erection multiple times within a 36-hour period.
Looking for erectile dysfunction treatment?
Is Tadalafil suitable for me?
Like all other ED medications, you will first need to complete an online consultation. From there our trained clinicians will assess your suitability for treatment and if appropriate will issue you with a prescription. For more information or to begin an online consultation for Tadalafil visit our online clinic.
Can I eat or drink alcohol with Tadalafil?
Yes, unlike some other ED treatments, food does not typically impact the effectiveness of Tadalafil. However, it is not advisable to drink more than one or two units of alcohol while taking the treatment.
Can I try Tadalafil?
Our online doctor service offers three pack sizes of Tadalafil. These range from a pack of 4, 8 or 16. If you’re interested in trying Tadalafil, then you should consider opting in for the 4-pack or 8-pack options. Remember that it is advised to use an ED medication on 8 separate occasions before increasing the dosage or trying a different medication.
Will there be a generic daily dose of Tadalafil?
You can get Tadalafil daily using our Online Doctor service.
Where can I obtain Tadalafil?
Tadalafil is available from LloydsPharmacy Online Doctor through our erectile dysfunction clinic.
Here you can compare the benefits, active ingredients and prices of different ED tablets before requesting the one you’d prefer. We operate a safe, discreet, regulated online service.
To ensure you can take your ED medicine safely, we require you to complete a short questionnaire to assess your medical history. This will be reviewed by one of our NHS-experienced clinicians and you’ll receive a message via your Patient Record to confirm you can order your treatment.
Can my ED repeat prescription be changed to Tadalafil?
If you are already an Online Doctor patient, then you can request to have your prescription changed via your patient record. If suitable, one of our clinicians will make Tadalafil available to you. In some instances, you may be required to start a new consultation for Tadalafil.

Which animal has the highest testosterone level?

which animal has the highest testosterone level?

What animal has the most testosterone?

The bull shark (Carcharhinus leucas), also known as the Zambezi shark (informally zambi) in Africa and Lake Nicaragua shark in Nicaragua, is a species of requiem shark commonly found worldwide in warm, shallow waters along coasts and in rivers.

Bull shark – Wikipedia

‘ testosterone levels are believed to be the highest in the animal kingdom. With 358 ng/ml (nanograms per milliliter) one shark tested even higher than a male African Elephant in heat with 64.4 gn/ml.

What animal has the lowest testosterone?

Pregnenolone concentrations are of equal height in all animals, testosterone is lowest in the cat and stallion. In the latter species the estradiol/testosterone ratio is spectacular high.

Do humans have higher testosterone than lions?

According to a study (see image below), captive lions in India had about 1849 pg/ml (picograms per milliliter) when their testosterone levels were measured. Human levels tend to be measured in nanograms per deciliter, so we must make a conversion. 1849 pg/ml = 184.9 ng/dl.

How much testosterone does a bull have?

Testosterone levels in three sexually mature bulls ranged from 0.2 to 2.7 ng/ml with a mean of 0.6 ± 0.2 ng/ml.

What is the highest natural testosterone?

As mentioned earlier, the normal range for testosterone is 270 to 1,000 ng/dl. If your assays indicate that your T level is lurking somewhere below 270 ng/dl, you may be silently suffering from hypogonadism. Much less likely is the opposite scenario: a T score that tops 1,000 ng/dl.

Testosterone Factor | Explorer

Do taller guys have more testosterone?

Despite being a sexually dimorphic trait in humans, height does not appear strongly and consistently related to circulating testosterone levels in adult men (Kowal et al., 2021) .

Do bigger guys have more testosterone?

One study, for example, found that compared to men with a healthy weight, obese men were more than 8x as likely to have a low testosterone level. And obesity holds the title as the most effective predictor of low testosterone in men – out of many possible risk factors. Shop At-Home Testosterone Test Today!

How much sperm is in a straw of bull?

These changes were shown as variations in NRR, which is defined as the number of bovines that were inseminated and did not return to service within a specific period. The study revealed 2.5 and 20 million bull spermatozoa per straw were optimum for liquid and cryopreserved semen, respectively.

What is the testosterone level of a grizzly bear?

General patterns. Overall, the median cortisol concentration was 8.1 pg/mg [range: 5.3–26.1] in 113 hair samples, the median testosterone was 5.6 pg/mg [range: 3.1–21.1] in 112 samples, and the median progesterone was 26.2 pg/mg [range: 9.1–46.2] in 27 samples.

What is the testosterone level in tigers?

Levels for the male Siberian tigers ranged from 1,329.1 to 1,760.8 pg/ml. Testosterone levels for the female tigers were 436.8 and 852.7 pg/ml, respectively.

Did ancient man have more testosterone?

They found that nearly all the skulls belonging to people who lived more than 80,000 years ago show evidence of testosterone levels that were far higher than any modern-day human’s. These high hormone levels may have made social cooperation and community-building more difficult.

Where is most of a man’s testosterone?

What is testosterone? Testosterone is a hormone that your gonads (sex organs) mainly produce. More specifically, the testicles in people assigned male at birth (AMAB) and the ovaries in people assigned female at birth (AFAB) produce testosterone.

Did cavemen have more testosterone?

New fossil research conducted by British and Canadian scientists suggests that our cave-dwelling ancestors had far higher testosterone levels than guys today.

Which gender has more testosterone?

Although testosterone exists and functions similarly in women and men, men have markedly higher average testosterone than women. This difference in testosterone is widely presumed to be a sex difference, that is, one that reflects maleness and femaleness caused by innate and evolved influences (3).

What is more powerful than testosterone?

Dihydrotestosterone is many times more potent than testosterone, and many of the effects that testosterone has in the body only happen after it is converted to dihydrotestosterone.

What food has the most testosterone?

  1. Ginger. Share on Pinterest Ginger may help increase testosterone levels and improve male fertility. .
  2. Oysters. .
  3. Pomegranates. .
  4. Fortified plant milks. .
  5. Leafy green vegetables. .
  6. Fatty fish and fish oil. .
  7. Extra-virgin olive oil. .
  8. Onions.

Who would win in a fight a gorilla or a bear?

Being close to the bear means being close to the mouth full of gnashing teeth and at least five claws ready to tear the gorilla apart with one swipe. With the bear’s massive body, superior muscle, surprising speed and evolutionary armory, there really isn’t any way a gorilla wins the fight.

What animal beats a grizzly bear?

In the battle of the grizzly bear vs tiger, a Siberian tiger would win a fight against a grizzly bear. The Siberian tiger is an ambush predator, and it’s the only big cat that comes close to the grizzly bear in terms of size and power.

How many times stronger is a grizzly than a man?

What animal has the most sperm?

Among the largest ejaculates relative to body size belongs to the boar Sus scrofa. Lüpold said that males of this boar “seem to produce ejaculates of over 50 billion sperm, which is well over 100 times a human ejaculate.” European hare males also have some of the greatest sperm numbers relative to their body size.

How much sperm is let out?

A fertile male human ejaculates between 2 and 5 mililiters(ml) of semen (on average about a teaspoon). In each ml there are normally about 100 million sperm. If the concentration falls below 20 million sperm per mililiter there is usually some trouble with fertility.

How much sperm is in a baby?

Even though only one sperm is needed for fertilization, most sperm cells will not survive the journey from the testicle to the uterus. Of the 200 million sperm deposited near the cervix in an average ejaculation, only 100,000 make it to the womb.

Does a deep voice mean high testosterone?

“However,” he says, “evidence suggests men evolved deeper voices mainly for intimidating other men rather than attracting women.” Studies show that men with deeper voices tend to have higher testosterone levels (an indicator of dominance) and a more athletic body type.

What are signs of high testosterone in males?

  • acne.
  • aggressive or risk-taking behaviors.
  • excessive body hair.
  • headaches.
  • heart or liver problems.
  • high blood pressure (hypertension)
  • high sex drive (libido)
  • increased appetite.

What age do males produce the most testosterone?

There was an age-related decline in testosterone levels, with 25- to 29-year- old men having the highest mean testosterone (514 ng/dL) and 40- to 44-year-old men having the lowest mean testosterone (430 ng/dL; Fig. 2).

Tadalafil 40 mg

tadalafil 40 mg

Label: TADALAFIL tablet.
These highlights do not include all the information needed to use TADALAFIL TABLETS safely and effectively. See full prescribing information for TADALAFIL TABLETS.
TADALAFIL tablets, for oral administration Initial U.S. Approval: 2003.
INDICATIONS AND USAGE.
Tadalafil is a phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II to III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%). (1.1)
DOSAGE AND ADMINISTRATION.
40 mg once daily, with or without food. (2.1) Dividing the dose (40 mg) over the course of the day is not recommended. (2.1) Use with ritonavir requires dosage adjustments. (2.4)
DOSAGE FORMS AND STRENGTHS.
CONTRAINDICATIONS.
Concomitant organic nitrates (4.1) Concomitant Guanylate Cyclase (GC) Stimulators (4.2) History of known serious hypersensitivity reaction to tadalafil tablets or CIALIS (4.3)
WARNINGS AND PRECAUTIONS.
Hypotension: Carefully consider whether patients with certain underlying cardiovascular disease could be adversely affected by vasodilatory effects of tadalafil. Not recommended in patients with pulmonary veno-occlusive disease. (5.1, 5.2) Effects on the eye: Sudden loss of vision could be a sign of non-arteritic ischemic optic neuropathy (NAION) and may be permanent. (5.3) Hearing impairment: Cases of sudden decrease or loss of hearing have been reported with CIALIS. (5.4) Concomitant PDE5 inhibitors: Avoid use with CIALIS or other PDE5 inhibitors. (5.5) Prolonged erection: Advise patients to seek emergency treatment if an erection lasts >4 hours. (5.6)
ADVERSE REACTIONS.
The most common adverse reaction is headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE.
1.1 Pulmonary Arterial Hypertension.
2 DOSAGE AND ADMINISTRATION.
2.1 Pulmonary Arterial Hypertension.
2.2 Dose Adjustment in Renal Impairment.
2.3 Dose Adjustment in Hepatic Impairment.
2.4 Dose Adjustments for Use with Ritonavir.
3 DOSAGE FORMS AND STRENGTHS.
4 CONTRAINDICATIONS.
4.1 Concomitant Organic Nitrates.
4.2 Concomitant Guanylate Cyclase (GC) Stimulators.
4.3 Hypersensitivity Reactions.
5 WARNINGS AND PRECAUTIONS.
5.1 Hypotension.
5.2 Worsening Pulmonary Vascular Occlusive Disease.
5.3 Visual Loss.
5.4 Hearing Impairment.
5.5 Combination with Other PDE5 Inhibitors.
5.6 Prolonged Erection.
6 ADVERSE REACTIONS.
6.1 Clinical Trials Experience.
6.2 Postmarketing Experience.
7 DRUG INTERACTIONS.
7.1 Nitrates.
7.2 Alpha-Blockers.
7.3 Antihypertensives.
7.4 Alcohol.
7.5 CYP3A Inhibitors/Inducers.
8 USE IN SPECIFIC POPULATIONS.
8.1 Pregnancy.
8.2 Lactation.
8.3 Females and Males of Reproductive Potential.
8.4 Pediatric Use.
8.5 Geriatric Use.
8.6 Renal Impairment.
8.7 Hepatic Impairment.
10 OVERDOSAGE.
11 DESCRIPTION.
12 CLINICAL PHARMACOLOGY.
12.1 Mechanism of Action.
12.2 Pharmacodynamics.
12.3 Pharmacokinetics.
13 NONCLINICAL TOXICOLOGY.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility.
13.2 Animal Toxicology and/or Pharmacology.
14 CLINICAL STUDIES.
14.1 Tadalafil for Pulmonary Arterial Hypertension.
14.2 Long-Term Treatment of Pulmonary Arterial Hypertension.
16 HOW SUPPLIED/STORAGE AND HANDLING.
16.1 How Supplied.
16.2 Storage.
17 PATIENT COUNSELING INFORMATION.
1.1 Pulmonary Arterial Hypertension.
Tadalafil tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II to III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%).
2.1 Pulmonary Arterial Hypertension.
The recommended dose of tadalafil tablets is 40 mg (two 20 mg tablets) taken once daily with or without food. Dividing the dose (40 mg) over the course of the day is not recommended.
2.2 Dose Adjustment in Renal Impairment.
Mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min): Start dosing at 20 mg once daily. Increase to 40 mg once daily based on individual tolerability. Severe (creatinine clearance.
2.3 Dose Adjustment in Hepatic Impairment.
Mild or moderate (Child Pugh Class A or B): Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis, consider a starting dose of 20 mg once per day. Severe (Child Pugh Class C): Patients with severe hepatic cirrhosis have not been studied. Avoid use of tadalafil tablets [see Use in Specific Populations (8.7)] .
2.4 Dose Adjustments for Use with Ritonavir.
Co-administration of Tadalafil Tablets in Patients on Ritonavir In patients receiving ritonavir for at least one week, start tadalafil tablets at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)] . Co-administration of Ritonavir in Patients on Tadalafil Tablets Avoid use of tadalafil tablets during the initiation of ritonavir. Stop tadalafil tablets at least 24 hours prior to starting ritonavir. After at least one week following the initiation of ritonavir, resume tadalafil tablets at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)] .
20 mg tablets are yellow colored, oval shaped, film-coated tablets debossed with ‘58’ on one side and ‘L’ on the other side.
4.1 Concomitant Organic Nitrates.
Tadalafil tablets are contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Do not use nitrates within 48 hours of the last dose of tadalafil tablets. Tadalafil tablets potentiate the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and tadalafil tablets on the nitric oxide/cGMP pathway [see Clinical Pharmacology (12.2)] .
4.2 Concomitant Guanylate Cyclase (GC) Stimulators.
Coadministration of GC stimulators such as riociguat with tadalafil tablets are contraindicated. Tadalafil tablets may potentiate the hypotensive effects of GC stimulators.
4.3 Hypersensitivity Reactions.
Tadalafil tablets are contraindicated in patients with a known serious hypersensitivity to tadalafil tablets or CIALIS. Hypersensitivity reactions have been reported, including Stevens-Johnson syndrome and exfoliative dermatitis [see Adverse Reactions (6.2)] .
5.1 Hypotension.
Tadalafil has vasodilatory properties that may result in transient decreases in blood pressure. Prior to prescribing tadalafil, carefully consider whether patients with underlying cardiovascular disease could be affected adversely by such vasodilatory effects. Patients with preexisting hypotension, with autonomic dysfunction, with left ventricular outflow obstruction, may be particularly sensitive to the actions of vasodilators.
5.2 Worsening Pulmonary Vascular Occlusive Disease.
Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Since there are no clinical data on administration of tadalafil to patients with veno-occlusive disease, administration of tadalafil to such patients is not recommended. Should signs of pulmonary edema occur when tadalafil is administered, the possibility of associated PVOD should be considered.
5.3 Visual Loss.
When used to treat erectile dysfunction, non-arteritic anterior ischemic optic neuropathy (NAION), a cause of decreased vision including permanent loss of vision, has been reported postmarketing in temporal association with the use of phosphodiesterase type 5 (PDE-5) inhibitors, including tadalafil. Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, including but not necessarily limited to: low cup to disc ratio (“crowded disc”), age over 50, diabetes, hypertension, coronary artery disease, hyperlipidemia, and smoking. Based on published literature, the annual incidence of NAION is 2.5 to 11.8 cases per 100,000 in males aged ≥50 in the general population. An observational case-crossover study evaluated the risk of NAION when PDE5 inhibitor use, as a class, typical of erectile dysfunction treatment, occurred immediately before NAION onset (within 5 half-lives), compared to PDE5 inhibitor use in a prior time period. The results suggest an approximate 2-fold increase in the risk of NAION, with a risk estimate of 2.15 (95% CI 1.06, 4.34). A similar study reported a consistent result, with a risk estimate of 2.27 (95% CI 0.99, 5.20). Other risk factors for NAION, such as the presence of “crowded” optic disc, may have contributed to the occurrence of NAION in these studies. Patients with known hereditary degenerative retinal disorders, including retinitis pigmentosa, were not included in the clinical trials, and use in these patients is not recommended.
5.4 Hearing Impairment.
Cases of sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness, have been reported in patients taking tadalafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors [see Adverse Reactions (6.2)].
5.5 Combination with Other PDE5 Inhibitors.
Tadalafil is also marketed for erectile dysfunction. The safety and efficacy of taking tadalafil together with another PDE5 inhibitor has not been studied. Inform patients taking tadalafil not to take other PDE5 inhibitors.
5.6 Prolonged Erection.
There have been reports of prolonged erections greater than 4 hours and priapism (painful erections greater than 6 hours in duration) for this class of compounds. Patients with conditions that might predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia), or in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) are at an increased risk. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.
6.1 Clinical Trials Experience.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Tadalafil was administered to 398 patients with PAH during clinical trials worldwide. In trials of tadalafil, a total of 311 and 251 subjects have been treated for at least 182 days and 360 days, respectively. The overall rates of discontinuation because of an adverse event (AE) in the placebo-controlled trial were 9% for tadalafil 40 mg and 15% for placebo. The rates of discontinuation because of AEs, other than those related to worsening of PAH, in patients treated with tadalafil 40 mg was 4% compared to 5% in placebo-treated patients.
In the placebo-controlled study, the most common AEs were generally transient and mild to moderate in intensity. Table 1 presents treatment-emergent adverse events reported by ≥9% of patients in the tadalafil 40 mg group and occurring more frequently than with placebo.
Table 1: Treatment-Emergent Adverse Events Reported by ≥9% of Patients in Tadalafil and More Frequent than Placebo by 2% EVENT Placebo (%) (N=82) Tadalafil 20 mg (%) (N=82) Tadalafil 40 mg (%) (N=79) Headache 15 32 42 Myalgia 4 9 14 Nasopharyngitis 7 2 13 Flushing 2 6 13 Respiratory Tract Infection (Upper and Lower) 6 7 13 Pain in Extremity 2 5 11 Nausea 6 10 11 Back Pain 6 12 10 Dyspepsia 2 13 10 Nasal Congestion (Including sinus congestion) 1 0 9.
6.2 Postmarketing Experience.
The following adverse reactions have been identified during post-approval use of tadalafil. These events have been chosen for inclusion either because of their seriousness, reporting frequency, lack of clear alternative causation, or a combination of these factors.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. The list does not include adverse events that are reported from clinical trials and that are listed elsewhere in this section.
Cardiovascular and cerebrovascular — Serious cardiovascular events, including myocardial infarction, sudden cardiac death, stroke, chest pain, palpitations, and tachycardia, have been reported postmarketing in temporal association with the use of tadalafil [see Contraindications (4.1)] . Most, but not all, of these patients had preexisting cardiovascular risk factors. Many of these events were reported to occur during or shortly after sexual activity, and a few were reported to occur shortly after the use of tadalafil without sexual activity. Others were reported to have occurred hours to days after the use of tadalafil and sexual activity. It is not possible to determine whether these events are related directly to tadalafil, to sexual activity, to the patient’s underlying cardiovascular disease, to a combination of these factors, or to other factors.
Body as a whole — Hypersensitivity reactions including urticaria, Stevens–Johnson syndrome, and exfoliative dermatitis.
Nervous — Migraine, seizure and seizure recurrence, and transient global amnesia.
Ophthalmologic — Visual field defect, retinal vein occlusion, retinal artery occlusion, and NAION [see Warnings and Precautions (5.3) and Patient Counseling Information (17)].
Otologic — Cases of sudden decrease or loss of hearing have been reported postmarketing in temporal association with the use of PDE5 inhibitors, including tadalafil. In some of the cases, medical conditions and other factors were reported that may have also played a role in the otologic adverse events. In many cases, medical follow-up information was limited. It is not possible to determine whether these reported events are related directly to the use of tadalafil, to the patient’s underlying risk factors for hearing loss, a combination of these factors, or to other factors [see Warnings and Precautions (5.4) and Patient Counseling Information (17)] .
7.1 Nitrates.
Administration of nitrates within 48 hours after the last dose of tadalafil is contraindicated [see Contraindications (4.1)] .
7.2 Alpha-Blockers.
PDE5 inhibitors, including tadalafil, and alpha–adrenergic blocking agents are both vasodilators with blood-pressure-lowering effects. When vasodilators are used in combination, an additive effect on blood pressure may be anticipated. Clinical pharmacology studies have been conducted with coadministration of tadalafil with doxazosin, alfuzosin or tamsulosin [see Clinical Pharmacology (12.2)] .
7.3 Antihypertensives.
PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Clinical pharmacology studies were conducted to assess the effect of tadalafil on the potentiation of the blood–pressure–lowering effects of selected antihypertensive medications (amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalapril, and metoprolol). Small reductions in blood pressure occurred following coadministration of tadalafil with these agents compared with placebo [see Clinical Pharmacology (12.2)] .
7.4 Alcohol.
Both alcohol and tadalafil, a PDE5 inhibitor, act as mild vasodilators. When mild vasodilators are taken in combination, blood pressure–lowering effects of each individual compound may be increased. Substantial consumption of alcohol (e.g., 5 units or greater) in combination with tadalafil can increase the potential for orthostatic signs and symptoms, including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. Tadalafil (10 mg or 20 mg) did not affect alcohol plasma concentrations and alcohol did not affect tadalafil plasma concentrations [See Clinical Pharmacology (12.2)] .
7.5 CYP3A Inhibitors/Inducers.
Ritonavir Ritonavir initially inhibits and later induces CYP3A, the enzyme involved in the metabolism of tadalafil. At steady state of ritonavir (about 1 week), the exposure to tadalafil is similar as in the absence of ritonavir [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)] . Potent Inhibitors of CYP3A Tadalafil is metabolized predominantly by CYP3A in the liver. In patients taking potent inhibitors of CYP3A such as ketoconazole, and itraconazole, avoid use of tadalafil [see Clinical Pharmacology (12.3)] . Potent Inducers of CYP3A For patients chronically taking potent inducers of CYP3A, such as rifampin, avoid use of tadalafil [see Clinical Pharmacology (12.3)] .
8.1 Pregnancy.
Risk Summary Limited data from case series with tadalafil use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats or mice during organogenesis at exposures 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day based on AUC (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death. Data Animal Data Tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. Animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at unbound tadalafil exposures up to 7 times the exposure at the maximum recommended human dose (MRHD) of 40 mg/day during organogenesis based on AUC. In one of two perinatal/postnatal developmental studies in rats, a reduction of postnatal pup survival was observed at dose levels of 60, 200 and 1000 mg/kg. The no-observed-effect-level (NOEL) for developmental toxicity was 30 mg/kg, which provided maternal exposure to unbound tadalafil concentrations approximately 5 times the exposure at the MRHD based on AUC. Signs of maternal toxicity occurred at doses greater than 200 mg/kg/day, which produced AUCs greater than 8 times the exposure at the MRHD. Surviving offspring had normal development and reproductive performance.
8.2 Lactation.
Risk Summary There are no data on the presence of tadalafil and/or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4-times that found in the plasma. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tadalafil and any potential adverse effects on the breastfed child from tadalafil or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential.
Infertility Males Based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. There was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone. The clinical significance of the decreased sperm concentrations in the two studies is unknown. There have been no studies evaluating the effect of tadalafil on fertility in men or women [see Clinical Pharmacology (12.2)] .
8.4 Pediatric Use.
8.5 Geriatric Use.
Of the total number of subjects in the clinical study of tadalafil for pulmonary arterial hypertension, 28 percent were 65 and over, while 8 percent were 75 and over. No overall differences in safety were observed between subjects over 65 years of age compared to younger subjects or those over 75 years of age. No dose adjustment is warranted based on age alone; however, a greater sensitivity to medications in some older individuals should be considered [See Clinical Pharmacology (12.3)] .
8.6 Renal Impairment.
For patients with mild or moderate renal impairment, start tadalafil at 20 mg once daily. Increase the dose to 40 mg once daily based upon individual tolerability [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)] . In patients with severe renal impairment, avoid use of tadalafil because of increased tadalafil exposure (AUC), limited clinical experience, and the lack of ability to influence clearance by dialysis [see Clinical Pharmacology (12.3)] .
8.7 Hepatic Impairment.
Because of limited clinical experience in patients with mild to moderate hepatic cirrhosis (Child-Pugh Class A or B), consider a starting dose of tadalafil 20 mg once daily. Patients with severe hepatic cirrhosis (Child-Pugh Class C) have not been studied, thus avoid use of tadalafil in such patients [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3)] .
Single doses up to 500 mg have been given to healthy male subjects, and multiple daily doses up to 100 mg have been given to male patients with erectile dysfunction. Adverse reactions were similar to those seen at lower doses. Doses greater than 40 mg have not been studied in patients with pulmonary arterial hypertension. In cases of overdose, standard supportive measures should be adopted as needed. Hemodialysis contributes negligibly to tadalafil elimination.
Tadalafil, an oral treatment for pulmonary arterial hypertension, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)–specific phosphodiesterase type 5 (PDE5). Tadalafil has the molecular formula C 22 H 19 N 3 O 4 representing a molecular weight of 389.41. The structural formula is:
The chemical designation is pyrazino[1′,2′:1,6]pyrido[3,4–b]indole-1,4-dione, 6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. It is a white or almost white powder that is practically insoluble in water and very slightly soluble in ethanol. Tadalafil Tablets USP are available as yellow colored, oval shaped, film-coated tablets for oral administration. Each tablet contains 20 mg of tadalafil USP and the following inactive ingredients: colloidal silicon dioxide, copovidone, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyoxyl 40 hydrogenated castor oil, talc, titanium dioxide, triacetin, and yellow iron oxide.
12.1 Mechanism of Action.
Tadalafil is an inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary arterial hypertension is associated with impaired release of nitric oxide by the vascular endothelium and consequent reduction of cGMP concentrations in the pulmonary vascular smooth muscle. PDE5 is the predominant phosphodiesterase in the pulmonary vasculature. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in relaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed. Studies in vitro have demonstrated that tadalafil is a selective inhibitor of PDE5. PDE5 is found in pulmonary vascular smooth muscle, visceral smooth muscle, corpus cavernosum, skeletal muscle, platelets, kidney, lung, cerebellum, and pancreas.
In vitro studies have shown that the effect of tadalafil is more potent on PDE5 than on other phosphodiesterases. These studies have shown that tadalafil is >10,000–fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs. Tadalafil is >10,000–fold more potent for PDE5 than for PDE3, an enzyme found in the heart and blood vessels. Additionally, tadalafil is 700–fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Tadalafil is >9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10. Tadalafil is 14–fold more potent for PDE5 than for PDE11A1 and 40–fold more potent for PDE5 than for PDE11A4, two of the four known forms of PDE11. PDE11 is an enzyme found in human prostate, testes, skeletal muscle and in other tissues. In vitro , tadalafil inhibits human recombinant PDE11A1 and, to a lesser degree, PDE11A4 activities at concentrations within the therapeutic range. The physiological role and clinical consequence of PDE11 inhibition in humans have not been defined.
12.2 Pharmacodynamics.
Effects on Blood Pressure When Administered with Nitrates In clinical pharmacology studies, tadalafil (5 to 20 mg) was shown to potentiate the hypotensive effect of nitrates. Do not use tadalafil in patients taking any form of nitrates [see Contraindications (4.1)] . A double–blind, placebo–controlled, crossover study in 150 male subjects at least 40 years of age (including subjects with diabetes mellitus and/or controlled hypertension) assessed the interaction between nitroglycerin and tadalafil. Subjects received daily doses of tadalafil 20 mg or matching placebo for 7 days and then were given a single dose of 0.4 mg sublingual nitroglycerin (NTG) at pre–specified timepoints following their last dose of tadalafil (2, 4, 8, 24, 48, 72, and 96 hours after tadalafil). A significant interaction between tadalafil and NTG was observed at each timepoint up to and including 24 hours. At 48 hours, by most hemodynamic measures, the interaction between tadalafil and NTG was not observed, although a few more tadalafil subjects compared to placebo experienced greater blood–pressure lowering effects at this timepoint. After 48 hours, the interaction was not detectable [See Contraindications (4.1)] . Effects on Blood Pressure . The effects of tadalafil on blood pressure alone and administered with antihypertensives, alcohol, and alpha-blockers is shown in Figure 1. a In some subjects, postural dizziness and orthostatic hypotension were observed. When tadalafil was administered with lower doses of alcohol (0.6 g/kg), hypotension was not observed, and dizziness occurred at a similar frequency to alcohol alone. b In studies of tadalafil co-administration with doxazosin, the number of subjects with potentially clinically significant standing blood pressure decreases was greater for the combination. Some patients had symptoms associated with the decrease in blood pressure including syncope. Figure 1: Effects of Tadalafil on Blood Pressure Effects on Cardiac Electrophysiology The effect of a single 100 mg dose of tadalafil (2.5 times the recommended dose) on the QT interval was evaluated at the time of peak tadalafil concentration in a randomized, double–blinded, placebo, and active–controlled (intravenous ibutilide) crossover study in 90 healthy males aged 18 to 53 years. The mean change in QT c (Fridericia QT correction) for tadalafil, relative to placebo, was 3.5 milliseconds (two–sided 90% CI=1.9, 5.1). The mean change in QT c (Individual QT correction) for tadalafil, relative to placebo, was 2.8 milliseconds (two–sided 90% CI=1.2, 4.4). In this study, the mean increase in heart rate associated with a 100 mg dose of tadalafil compared to placebo was 3.1 beats per minute. Effects on Exercise Stress Testing The effects of tadalafil on cardiac function, hemodynamics, and exercise tolerance were investigated in a single clinical pharmacology study. In this blinded crossover trial, 23 subjects with stable coronary artery disease and evidence of exercise–induced cardiac ischemia were enrolled. The primary endpoint was time to cardiac ischemia. The mean difference in total exercise time was 3 seconds (tadalafil 10 mg minus placebo), which represented no clinically meaningful difference. Further statistical analysis demonstrated that tadalafil was similar to placebo with respect to time to ischemia. Of note, in this study, in some subjects who received tadalafil followed by sublingual nitroglycerin in the post–exercise period, clinically significant reductions in blood pressure were observed, consistent with the augmentation by tadalafil of the blood–pressure–lowering effects of nitrates. Effects on Vision Single oral doses of PDE inhibitors have demonstrated transient dose-related impairment of color discrimination (blue/green), using the Farnsworth–Munsell 100–hue test, with peak effects near the time of peak plasma levels. This finding is consistent with the inhibition of PDE6, which is involved in phototransduction in the retina. In a study to assess the effects of a single dose of tadalafil 40 mg on vision (N=59), no effects were observed on visual acuity, intraocular pressure, or pupillometry. Across all clinical studies with tadalafil, reports of changes in color vision were rare ( Effects on Sperm Characteristics Three studies were conducted in men to assess the potential effect on sperm characteristics of tadalafil 10 mg (one 6-month study) and 20 mg (one 6-month and one 9-month study) administered daily. There were no adverse effects on sperm morphology or sperm motility in any of the three studies. In the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months, results showed a decrease in mean sperm concentrations relative to placebo, although these differences were not clinically meaningful. This effect was not seen in the study of 20 mg tadalafil taken for 6 months. In addition there was no adverse effect on mean concentrations of reproductive hormones, testosterone, luteinizing hormone or follicle stimulating hormone with either 10 or 20 mg of tadalafil compared to placebo. Dose-Response Relationship Dose-response relationships, between 20 mg and 40 mg, were not observed for 6-minute walk distance or pulmonary vascular resistance (PVR) in subjects with PAH in the placebo-controlled study. Median change from baseline in 6-minute walk distance was 32 meters and 35 meters at 16 weeks in subjects receiving 20 mg and 40 mg daily, respectively. Mean change from baseline PVR was -254 dynes*sec*cm -5 and -209 dynes*sec*cm -5 at 16 weeks in patients receiving 20 mg and 40 mg daily, respectively.
12.3 Pharmacokinetics.
Over a dose range of 2.5 to 20 mg, tadalafil exposure (AUC) increases proportionally with dose in healthy subjects. In PAH patients administered between 20 and 40 mg of tadalafil, an approximately 1.5-fold greater AUC was observed indicating a less than proportional increase in exposure over the entire dose range of 2.5 to 40 mg. During tadalafil 20 and 40 mg once daily dosing, steady-state plasma concentrations were attained within 5 days, and exposure was approximately 1.3-fold higher than after a single dose. Absorption — After single oral-dose administration, the maximum observed plasma concentration (C max ) of tadalafil is achieved between 2 and 8 hours (median time of 4 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined. The rate and extent of absorption of tadalafil are not influenced by food; thus tadalafil may be taken with or without food. Distribution — The mean apparent volume of distribution following oral administration is approximately 77 L, indicating that tadalafil is distributed into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to proteins. Metabolism — Tadalafil is predominantly metabolized by CYP3A to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form the methylcatechol and methylcatechol glucuronide conjugate, respectively. The major circulating metabolite is the methylcatechol glucuronide. Methylcatechol concentrations are less than 10% of glucuronide concentrations. In vitro data suggests that metabolites are not expected to be pharmacologically active at observed metabolite concentrations. Elimination — Following 40 mg, the mean oral clearance for tadalafil is 3.4 L/hr and the mean terminal half-life is 15 hours in healthy subjects. In patients with pulmonary hypertension not receiving concomitant bosentan, the mean oral clearance for tadalafil is 1.6 L/hr, and the mean terminal half-life is 35 hours. Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose). Population pharmacokinetics — In patients with pulmonary hypertension not receiving concomitant bosentan, the average tadalafil exposure at steady-state following 40 mg was 26% higher when compared to those of healthy volunteers. The results suggest a lower clearance of tadalafil in patients with pulmonary hypertension compared to healthy volunteers. Geriatric patients In healthy male elderly subjects (65 years or over) after a 10 mg dose, a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) with no effect on C max was observed relative to that in healthy subjects 19 to 45 years of age. Renal impairment In clinical pharmacology studies using single-dose tadalafil (5 to 10 mg), tadalafil exposure (AUC) doubled in subjects with mild (creatinine clearance 51 to 80 mL/min) or moderate (creatinine clearance 31 to 50 mL/min) renal impairment. In subjects with end-stage renal disease on hemodialysis, there was a two-fold increase in C max and 2.7- to 4.1-fold increase in AUC following single-dose administration of 10 or 20 mg tadalafil, respectively. Exposure to total methylcatechol (unconjugated plus glucuronide) was 2- to 4-fold higher in subjects with renal impairment, compared to those with normal renal function. Hemodialysis (performed between 24 and 30 hours post-dose) contributed negligibly to tadalafil or metabolite elimination [see Dosage and Administration (2.2)] . Hepatic impairment In clinical pharmacology studies, tadalafil exposure (AUC) in subjects with mild or moderate hepatic impairment (Child-Pugh Class A or B) was comparable to exposure in healthy subjects when a dose of 10 mg was administered. There are no available data for doses higher than 10 mg of tadalafil in patients with hepatic impairment. Insufficient data are available for subjects with severe hepatic impairment (Child-Pugh Class C) [see Dosage and Administration (2.3)] . Patients with diabetes mellitus In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure (AUC) was reduced approximately 19% and C max was 5% lower than that observed in healthy subjects. No dose adjustment is warranted. Race Pharmacokinetic studies have included subjects from different ethnic groups, and no differences in the typical exposure to tadalafil have been identified. No dose adjustment is warranted. Gender In healthy female and male subjects following single and multiple-doses of tadalafil, no clinically relevant differences in exposure (AUC and C max ) were observed. No dose adjustment is warranted. Drug interaction studies Tadalafil is a substrate of and predominantly metabolized by CYP3A. Cytochrome P450 3A4 inhibitors Ketoconazole increased tadalafil exposure relative to the values for tadalafil alone (Figure 2). Although specific interactions have not been studied, other CYP3A inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. Ritonavir Ritonavir increased tadalafil 20–mg single-dose exposure relative to the values for tadalafil alone. Ritonavir inhibits and induces CYP3A, the enzyme involved in the metabolism of tadalafil, in a time-dependent manner. The initial inhibitory effect of ritonavir on CYP3A may be mitigated by a more slowly evolving induction effect so that after about 1 week of ritonavir twice daily, the exposure of tadalafil is similar in the presence of and absence of ritonavir [see Dosage and Administration (2.4) and Drug Interactions (7.5)] . Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure. Cytochrome P450 3A4 inducers Rifampin (600 mg daily), a CYP3A inducer, reduced tadalafil 10 mg single–dose exposure (AUC) by 88% and C max by 46%, relative to the values for tadalafil 10 mg alone [see Drug Interactions (7.5)] . Bosentan, a substrate of CYP2C9 and CYP3A and a moderate inducer of CYP3A, CYP2C9 and possibly CYP2C19, reduced tadalafil systemic exposure following multiple-dose co-administration (Figure 2). Although specific interactions have not been studied, other CYP3A inducers, such as carbamazepine, phenytoin, and phenobarbital, would likely decrease tadalafil exposure. Exposure changes of tadalafil following co-administration with other drugs are shown in Figure 2.
a Ritonavir is also a CYP2C9/CYP2C19/CYP2D6 Inhibitor and CYP3A inducer. b [see Dosage and Administration (2.4) ] . c Bosentan is also a CYP2C9/CYP2C19 inducer. Figure 2: Impact of Other Drugs on the Pharmacokinetics of Tadalafil Cytochrome P450 substrates Tadalafil is not expected to cause clinically significant inhibition or induction of the clearance of drugs metabolized by cytochrome P450 (CYP) isoforms. Exposure changes of drugs following co-administration with tadalafil are shown in Figure 3. a A small augmentation (increase of 3 beats per minute) in heart rate was observed with theophylline. b Tadalafil (40 mg qd) had no clinically significant effect on exposure (AUC and C max ) of bosentan metabolites. c 95% CI Figure 3: Impact of Tadalafil on the Pharmacokinetics of Other Drugs.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility.
Carcinogenesis — Tadalafil was not carcinogenic to rats or mice when administered daily for 2 years at doses up to 400 mg/kg/day. Systemic drug exposures, as measured by AUC of unbound tadalafil, were approximately 5–fold for mice, and 7– and 14–fold for male and female rats, respectively, the exposures at the maximum recommended human dose (MRHD) of 40 mg. Mutagenesis — Tadalafil was not mutagenic in the in vitro bacterial Ames assays or the forward mutation test in mouse lymphoma cells. Tadalafil was not clastogenic in the in vitro chromosomal aberration test in human lymphocytes or the in vivo rat micronucleus assays. Impairment of Fertility — There were no effects on fertility, reproductive performance or reproductive organ morphology in male or female rats given oral doses of tadalafil up to 400 mg/kg/day, a dose producing AUCs for unbound tadalafil of 6–fold for males or 17–fold for females the exposures at the MRHD of 40 mg. In beagle dogs given tadalafil daily for 3 to 12 months, there was treatment–related non–reversible degeneration and atrophy of the seminiferous tubular epithelium in the testes in 20 to 100% of the dogs that resulted in a decrease in spermatogenesis in 40 to 75% of the dogs at doses of ≥10 mg/kg/day. Systemic exposure (based on AUC) at no–observed–adverse-effect–level (NOAEL) (10 mg/kg/day) for unbound tadalafil was similar to that expected in humans at the MRHD of 40 mg.
There were no treatment–related testicular findings in rats or mice treated with doses up to 400 mg/kg/day for 2 years.
13.2 Animal Toxicology and/or Pharmacology.
Animal studies showed vascular inflammation in tadalafil–treated mice, rats, and dogs. In mice and rats, lymphoid necrosis and hemorrhage were seen in the spleen, thymus, and mesenteric lymph nodes at unbound tadalafil exposure of 1– to 17–fold the human exposure (AUCs) at the MRHD of 40 mg. In dogs, an increased incidence of disseminated arteritis was observed in 1– and 6-month studies at unbound tadalafil exposure of 0.5– to 38–fold the human exposure (AUC) at the MRHD of 40 mg. In a 12–month dog study, no disseminated arteritis was observed, but 2 dogs exhibited marked decreases in white blood cells (neutrophils) and moderate decreases in platelets with inflammatory signs at unbound tadalafil exposures of approximately 4– to 10–fold the human exposure at the MRHD of 40 mg. The abnormal blood–cell findings were reversible within 2 weeks upon removal of the drug.
14.1 Tadalafil for Pulmonary Arterial Hypertension.
A randomized, double-blind, 16 week placebo-controlled study was conducted in 405 patients with pulmonary arterial hypertension, defined as a resting mean pulmonary artery pressure (mPAP) ≥25 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) ≥3 Wood units via right heart catheterization. Allowed background therapy included bosentan (maintenance dosing up to 125 mg twice daily) and chronic anticoagulation. The use of prostacyclin or analogue, L-arginine, phosphodiesterase inhibitor, or other chronic PAH medications were not permitted. Subjects were randomly assigned to 1 of 5 treatment groups (tadalafil 2.5, 10, 20, 40 mg, or placebo) in a 1:1:1:1:1 ratio. Subjects had to be at least 12 years of age and had a diagnosis of PAH that was idiopathic, heritable, related to connective tissue disease, anorexigen use, human immunodeficiency virus (HIV) infection, associated with an atrial-septal defect, or associated with surgical repair of a congenital systemic-to-pulmonary shunt of least 1 year in duration (for example, ventricular septal defect, patent ductus arteriosus). Patients with a history of left-sided heart disease, severe renal insufficiency, or pulmonary hypertension related to conditions other than specified in the inclusion criteria were not eligible for enrollment. The mean age of all subjects was 54 years (range 14 to 90 years) with the majority of subjects being Caucasian (81%) and female (78%). PAH etiologies were predominantly idiopathic or heritable PAH (61%) and related to connective tissue disease (23%). More than half (53%) of the subjects in the study were receiving concomitant bosentan therapy. The majority of subjects had a World Health Organization (WHO) Functional Class III (65%) or II (32%). The mean baseline 6-minute walk distance (6-MWD) was 343 meters. Of the 405 subjects, 341 completed the study. The primary efficacy endpoint was the change from baseline at week 16 in 6-MWD ( see Figure 4). In the tadalafil 40 mg treatment group, the placebo-adjusted mean change increase in 6-MWD was 33 meters (95% C.I. 15 to 50 meters; p=0.0004). The improvement in 6-MWD was apparent at 8 weeks of treatment and then maintained at week 12 and week 16.
Figure 4: 6-Minute Walk Distance (meters) Mean Change from Baseline, with 95% Confidence Intervals Placebo-adjusted changes in 6-MWD at 16 weeks were evaluated in subgroups ( see Figure 5). In patients taking only tadalafil 40 mg (i.e., without concomitant bosentan), the placebo-adjusted mean change in 6-MWD was 44 meters. In patients taking tadalafil 40 mg and concomitant bosentan therapy, the placebo adjusted mean change in 6-MWD was 23 meters.
Figure 5: Placebo-adjusted Mean Change in 6-Minute Walk Distance (meters) of Tadalafil 40 mg, with 95% Confidence Intervals There was less clinical worsening (defined as death, lung transplantation, atrial septostomy, hospitalization because of worsening PAH, initiation of new PAH therapy [prostacyclin or analog, endothelin receptor antagonist, PDE5 inhibitor], or worsening WHO functional class) in the tadalafil 40 mg group compared to the placebo group and the groups that used lower doses of tadalafil.
Table 2: Number (percent) with Clinical Worsening a a Subjects may be counted in more than one category Tadalafil Placebo N=82 2.5 mg N=82 10 mg N=80 20 mg N=82 40 mg N=79 Total with clinical worsening 13 (16) 10 (12) 7 (9) 8 (10) 4 (5) Death 1 0 1 0 0 Hospitalization for worsening PAH 2 2 3 0 1 New PAH therapy 0 1 0 2 1 Worsening WHO class 11 10 6 6 3.
The Kaplan-Meier plot of times to clinical worsening is shown below in Figure 6.
14.2 Long-Term Treatment of Pulmonary Arterial Hypertension.
Patients (N=357) from the placebo-controlled study entered a long-term extension study. Of these, 311 patients have been treated with tadalafil for at least 6 months and 182 for 1 year (median exposure 356 days; range 2 days to 415 days). The survival rate in the extension study was 96.5 per 100 patient years. Without a control group, these data must be interpreted cautiously.
16.1 How Supplied.
Tadalafil Tablets USP 20 mg are yellow colored, oval shaped, film-coated tablets debossed with ‘58’ on one side and ‘L’ on the other side.
16.2 Storage.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Inform patients of contraindication of tadalafil with any use of organic nitrates or GC stimulators. Inform patients that tadalafil is also marketed as CIALIS for erectile dysfunction (ED) and for the signs and symptoms of benign prostatic hyperplasia (BPH). Advise patients taking tadalafil not to take CIALIS or other PDE5 inhibitors. Advise patients to seek immediate medical attention in the event of a sudden loss of vision in one or both eyes while taking tadalafil. Such an event may be a sign of NAION. Also discuss with patients that there is an increased risk of NAION in individuals who have already experienced NAION in one eye, including whether such individuals could be adversely affected by use of vasodilators such as PDE5 inhibitors. Advise patients to seek prompt medical attention in the event of sudden decrease or loss of hearing while taking tadalafil. These events may be accompanied by tinnitus and dizziness.
Medicines that treat chest pain (angina) Nitroglycerin in any form including tablets, patches, sprays, and ointments Other nitrate medicines (isosorbide mononitrate or dinitrate) Street drugs that are inhaled, called “poppers” (amyl nitrate, butyl nitrate or nitrite)
Ask your healthcare provider or pharmacist if you are not sure if you take a nitrate or guanylate cyclase stimulator medicine. What are tadalafil tablets? Tadalafil tablets are a prescription medicine used to treat pulmonary arterial hypertension (PAH, high blood pressure in your lungs) to improve your ability to exercise.
It is not known if tadalafil tablets are safe or effective in children. Who should not take tadalafil tablets? Do not take tadalafil tablets if you.
take any medicines called nitrates. use recreational drugs called “poppers” like amyl nitrate, butyl nitrate or nitrite. take any medicines called guanylate cyclase stimulators are allergic to tadalafil or any other ingredient in tadalafil tablets. See “ What are the ingredients in tadalafil tablets? ” at the end of this leaflet.
See “What is the most important information I should know about tadalafil tablets? ” What should I tell my healthcare provider before taking tadalafil tablets? Before taking tadalafil tablets, tell your healthcare provider about all of your medical conditions, including if you:
are allergic to tadalafil tablets or Cialis or any of its ingredients. See the end of this leaflet for a complete list of ingredients in tadalafil tablets. have pulmonary veno-occlusive disease (PVOD) have heart problems have low blood pressure have liver problems have kidney problems or get dialysis have retinitis pigmentosa, a rare genetic eye disease have ever had any sudden vision loss, including any damage to your optic nerve or NAION. have ever had hearing problems such as ringing in the ears, dizziness, or loss of hearing have a deformed penis shape or Peyronie’s disease have had an erection that lasted more than 4 hours have blood cell problems such as sickle cell anemia, multiple myeloma, or leukemia are pregnant or planning to become pregnant. Talk to your healthcare provider if you are pregnant or plan to become pregnant. are breastfeeding or plan to breast feed. If you breastfeed while taking tadalafil tablets, it is likely that tadalafil will pass into your breast milk. You and your healthcare provider should decide if you will take tadalafil tablets or breastfeed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Tadalafil tablets and other medicines may affect each other.
Especially tell your healthcare provider if you take any of these medicines * :
nitrates or guanylate cyclase stimulators (see “ What is the most important information I should know about tadalafil tablets? ”) alpha blockers, used to treat prostate disease and high blood pressure. Your blood pressure could suddenly drop. You could get dizzy or faint. protease inhibitors, used to treat HIV infection, such as ritonavir (Norvir ® , Kaletra ® ) ketoconazole (Extina ® , Xolegel ® , Ketozole ® , Nizoral A-D ® , Nizoral ® ) itraconazole (Sporanox ® ) erythromycin (several brand names exist. Please consult your healthcare provider to determine if you are taking this medicine) rifampin (Rifadin ® , Rifamate ® , Rifater ® , Rimactane ® ) bosentan (Tracleer ® ) phenobarbital, phenytoin (Dilantin ® ), carbamazepine (Tegretol ® ) CIALIS ® or other medicines or treatments for erectile dysfunction (impotence). Tadalafil tablets are also marketed as CIALIS for the treatment of male erectile dysfunction (ED, impotence) and for the signs and symptoms of benign prostatic hyperplasia (BPH, enlarged prostate). Do not take both tadalafil tablets and CIALIS. Do not take tadalafil tablets and other medicines or treatments for erectile dysfunction.
Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine. How should I take tadalafil tablets?
Take tadalafil tablets exactly as your healthcare provider tells you. Take tadalafil tablets at the same time every day. You should take both tablets at the same time, one after the other, every day. Do not split your dose. Tadalafil tablets can be taken with or without food. Do not change your dose or stop taking tadalafil tablets without speaking to your healthcare provider. If you take too much tadalafil, call your healthcare provider or go to an emergency department right away.
What should I avoid while taking tadalafil tablets? Do not have more than 4 alcohol-containing drinks in a short period of time while you take tadalafil tablets. Drinking too much alcohol can lower your blood pressure. You could get dizzy or faint. What are the possible side effects of tadalafil tablets? The following side effects were reported rarely in patients taking tadalafil:
Decreased eyesight or loss of vision in one or both eyes (NAION). If you notice a sudden decrease or loss of vision in one or both eyes, contact a healthcare provider right away. Sudden decrease or loss of hearing, sometimes with ringing in the ears and dizziness. If you notice a sudden decrease or loss of hearing, contact a healthcare provider right away. In men, an erection that lasts more than 4 hours (with or without pain). Talk to your healthcare provider or go to the emergency department right away. An erection that lasts more than 4 hours must be treated as soon as possible or you can have lasting damage to your penis, including the inability to have erections.
See “What is the most important information I should know about tadalafil tablets?” The most common side effects with tadalafil tablets include:
headache muscle pain getting red or hot in the face (flushing) nausea pain in the arms, legs, or back upset stomach stuffy or congested nose.
Tell your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of tadalafil tablets. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How Should I Store Tadalafil Tablets? Store tadalafil tablets at room temperature between 20° to 25°C (68° to 77°F). Keep tadalafil tablets and all medicines out of the reach of children. General Information about the safe and effective use of tadalafil tablets Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use tadalafil tablets for a condition for which it was not prescribed. Do not give tadalafil tablets to other people, even if they have the same symptoms you have. They may harm them.
This patient information leaflet summarizes the most important information about tadalafil tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about tadalafil tablets that is written for healthcare professionals. For more information, call Aurobindo Pharma USA, Inc. at 1-866-850-2876. What Are The Ingredients In Tadalafil Tablets? Active Ingredient: tadalafil.
Inactive Ingredients: colloidal silicon dioxide, copovidone, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyoxyl 40 hydrogenated castor oil, talc, titanium dioxide, triacetin, and yellow iron oxide.
This Patient Information has been approved by the U.S. Food and Drug Administration.
*The brands listed are trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited. The makers of these brands are not affiliated with and do not endorse Aurobindo Pharma Limited or its products.
Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520.
Manufactured by: Aurobindo Pharma Limited Hyderabad-500 032, India.
NDC 65862-880-60 Rx only Tadalafil Tablets USP 20 mg AUROBINDO 60 Tablets.

Cialis advertisement

cialis advertisement

Cialis Is Here.
If anyone has ever sat down to watch sports on a Sunday afternoon, Cialis is probably a common name. Cialis is the generic name for tadalfil, a prescription drug used to help with erectile dysfunction in men. In addition to this, Cialis can be used to treat a condition known as benign prostatic hyperplasia which is the enlargement of the prostate gland.
Growing up, I have always seen the very familiar commercials presenting a happy older couple doing romantic activities as an ad for Cialis. These commercials are almost so common that they are even shown during huge sports events, such as the super bowl, which is one of the most watched TV shows. Due to its extreme normality and popularity, I found myself interested in learning more about the actual risks and side effects of this common dru.
The company that works with Cialis is called Eli Lilly and Company. They operate under their core values, which are integrity, excellence, and respect for people. They do this through working with health care professionals and the people who will be taking their medication. Their mission statement is “We make medicines that help people live longer, healthier, more active lives.” When it comes to Cialis, it is expected that they act with integrity and make drugs that actually do what they say in a safe manner. Their mission statement gives the assumption that they will make sure the people who take their medications are safe and aware of the risks.
On the Cialis website, they are very clear about the risks and side effects associated with Cialis. This shows that Eli Lilly and Company are taking precautions and not lying to their customers or healthy providers. However, in the commercials these warnings are usually read very quickly towards the end and after the consumer may already be hooked on the idea of the product.
The Cialis website does go the extra mile with the awareness that people may be buying this product online through an online prescription and they take notice of this for their consumers. They give guidelines on how to make sure you are not buying counterfeit Cialis that could potentially harm the patient.
Who should look into Cialis?
The main audience for Cialis is men with erectile dysfunction. As stated previously, Cialis can also treat BPH, but the main issue is erectile dysfunction. Erectile dysfunction (ED) occurs in approximately 18 million men in the United States. Essentially, erectile dysfunction is the inability to get or keep an erection for sexual activity. It can be caused by many things, including heart disease. Obesity, tobacco use, and other related reasons. This many cause some men self-esteem issues, depression, and stress. Many Cialis commercials are targeted at older men, as this is a more common problem for them. A typical place to see a commercial for Cialis is during a sports program as those are views by society as male activities.
Active ingredients and risks.
According to Rx List, The chemical makeup of Cialis is “pyrazino[1´,2´:1,6]pyrido[3,4-b]indole-1,4-dione, 6-(1,3-benzodioxol-5- yl)-2,3,6,7,12,12a-hexahydro-2-methyl-, (6R,12aR)-. CIALIS (tadalafil) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Tadalafil has the empirical formula C22H19N3O4 representing a molecular weight of 389.41.”
You can buy Cialis for oral administration and each tablet contains 2.5, 5, 10, or 20 mg of tadalafill. It does contain the following inactive ingredients as well: croscarmellose sodium, hydroxypropyl cellulose, hypromellose, iron oxide, lactose monohydrate, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, talc, titanium dioxide, and triacetin.
As with most medications, Cialis does come with come risks. Most of these side effects are rare, but potentially can be very dangerous so users should alert their doctor if they notice any of these. Cialis can cause allergic reactions, chest pain, abnormal heartbeats, bad headaches, weakness, change or loss in eyesight, hearing loss, or muscle pain. The side effects can also be minor and may only be a slight headache or back pain. Runny or stuffy noses are common as well.
How the advertisements work.
Many Cialis commercials are of a man and a woman doing usual activities such as playing tennis or swimming. This is the company trying to relate to the audience on a personal level by showing people do activities that regular people can connect to. This allows the audience to feel connected and to normalize these kind of drugs. Another similar example is Viagra, which has the same effect but is slightly different. These commercials use the same approach. The couples in the commercials are generally very happy, this is to show the result of the drug.
Overall, Cialis has a few purposes. The risks and side effects are made well known, and for what the drug helps with, it seems like a fair trade if that is what someone is looking for. Cialis is not for everyone, so the user should really decide if it is worth it. It comes with a lot of side effects, so it is definitely not the safest route, but it may be the easiest. Alternative options include more physical activity as obesity is a leading cause of erectile dysfunction. However, these options do not work for all causes. I would recommend Cialis to anyone who is seeking to fix their medical problem but is willing to do a little research.

Men with too much testosterone

men with too much testosterone

Beware – too much testosterone could kill you!

A new study found that men who live the longest are those who have medium testosterone levels. High or low testosterone levels are linked to reduced mortality. Testosterone is a key male sex hormone involved in maintaining sex drive, sperm production and bone health. Physicians have long known that low testosterone levels can signal health problems, but the new study found men may not fare better when levels of the hormone rise too high.

‘Older men who had testosterone in the middle range survived longer than their counterparts who had either low or high levels of the hormone,’ the study’s lead author, Bu Beng Yeap, MBBS, FRACP, PhD, of the University of Western Australia, based in Fremantle Hospital, Western Australia, said. ‘When the body metabolizes testosterone, it produces dihydrotestosterone (DHT), which is tied to a lower risk of dying from ischemic heart disease. Having the right amount of testosterone and higher levels of DHT might indicate these men are in better health overall, or it could help them maintain good health as they grow older,’ the researcher said.

The population-based cohort study analyzed the mortality rate in a group of 3,690 community-dwelling men between the ages of 70 to 89 in Perth, Western Australia. Participants’ testosterone and DHT levels were measured between 2001 and 2004. Researchers analyzed the group’s survival rate as of December 2010.

Researchers divided the men into four groups based on their testosterone levels. Men with the lowest testosterone levels had the highest cumulative mortality rate, followed by the men with the highest testosterone levels. Men with circulating testosterone levels in the 9.8 to 15.8 nmol/L range tended to live longer. ‘Sex hormones are an important predictor of mortality in older men, but we haven’t determined if treatments to change testosterone and DHT levels can alter these outcomes,’ Yeap said.

The research is set to be published in The Endocrine Society’s Journal of Clinical Endocrinology and Metabolism.

What we’ve learned about testosterone till now?

More than 25 percent of urban Indian males have low testosterone hormones due to unhealthy lifestyles. However, lack of awareness means that many patients go undiagnosed, doctors say. ’Male Hypogonadism’ affects 26.1 percent of the working population of Indian men and is caused by unhealthy lifestyle, including smoking, consuming alcohol and junk food, high stress levels etc. The hormone plays a key role in masculine growth and development during puberty.

According to doctors, symptoms include decreased libido, impaired erectile function, muscle weakness, fatigue and depression. ‘It is an established clinical condition in medicine and in India the numbers are rising drastically over the years. However, many patients with this disorder go undiagnosed,’ Ajit Saxena, senior consultant urologist and andrologist, Apollo Indraprastha Hospitals, told IANS. ‘There is a clear need to increase the awareness of hypogonadism with the rising evidence suggesting a rise in the prevalence of the disorder in working population of Indian men,’ he added. Sadly, not many general physicians are aware of this disorder.

Testosterone, the primary male sex hormone, also keeps depression at bay. Now scientists have figured out how. Nicole Carrier and Mohamed Kabbaj of the Florida State University have found that a specific pathway in the brain’s hippocampus, involved in memory formation and stress response regulation, plays a major role in mediating the testosterone’s effects. Carrier and Kabbaj performed multiple experiments in neutered adult male rats. The rats developed depressive behaviour that was reversed with testosterone replacement, the journal Biological Psychiatry reports. They also ‘identified a molecular pathway called MAPK/ERK2 in the hippocampus that plays a major role in mediating the protective effects of testosterone’, said Kabbaj, according to a Florida statement.

It could be used as a male contraceptive

A hormonal gel combo applied daily to the skin showed promise as a male contraceptive by reducing sperm production, say US scientists. About 89 percent of men using the new combo of skin gels enriched with testosterone and a new synthetic progestin called Nestorone, reported very low sperm counts.

‘This is the first time that testosterone and Nestorone have been applied to the skin together to deliver adequate amounts of hormones that suppress sperm production,’ said principal investigator Christine Wang, professor at the University of California’s Los Angeles Biomedical Research Institute.

‘Men can use transdermal (skin) gels at home – unlike the usual injections and implants, which must be given in a health care provider’s office,’ added Wang, according to a California statement. Prior studies of male contraceptives that combined testosterone and progestin used progestin pills, implants or shots, according to Wang.