Overview Levitra (vardenafil) is one of several medications available today to treat erectile dysfunction (ED). With ED, a man has trouble getting an erection. He may also have trouble keeping an erection long enough for sexual activity. Alcohol can sometimes play a part in sexual activity, so it’s important to understand how a drug you take for ED can interact with alcohol.
Here’s what you need to know about Levitra, alcohol, ED, and your safety. Men who took the first ED medications were often told to avoid drinking alcohol while using their drugs. But today, several ED medications can be taken with alcohol. In general, Levitra is safe to use with alcohol. Studies have shown that there are no significant health effects when using the two together.
In addition to Levitra, Viagra and Edex are also safe to take if you drink. However, other ED drugs can still cause issues. For example, Cialis and Stendra can cause low blood pressure when used with large amounts of alcohol, so users are encouraged to have only a few drinks when using these medications.
- Whether you’re taking an ED medication or not, chronic alcohol use or misuse may prevent proper erectile function.
- Heavy alcohol consumption is one of the leading causes of ED, so taking Levitra while drinking heavily may be unhelpful at best.
- Even light drinking can sometimes cause problems with getting an erection.
Avoiding alcohol could be helpful for people having any kind of erectile problems, whether or not they’re taking medication for them. Read more: The effects of alcohol on the body » Although it’s generally safe to take with alcohol, Levitra does not mix well with certain medications and other substances.
- It’s important that you discuss all of the medications and supplements you’re taking with your doctor before you begin using Levitra.
- Certain prescription and over-the-counter medications can interact with Levitra and may even cause a dangerous increase in the effects of the medications.
- Blood pressure medications, including alpha blockers such as prazosin (Minipress), should not be taken with Levitra.
Nitrates, which are often used to treat angina (chest pain), should also be avoided. You should also stay away from street drugs called “poppers,” which contain nitrates. Other substances that may interact with Levitra include:
Herbal products: If you’re taking any supplements or herbs, especially St. John’s wort, tell your doctor before using Levitra.Grapefruit juice: Don’t drink grapefruit juice if you take Levitra. It can increase the amount of the drug in your body and cause harmful effects. High-fat meals: Taking Levitra with a high-fat meal can make the drug less effective.Tobacco: Tell your doctor if you smoke. Smoking may worsen ED, making Levitra less effective.
There’s no research that says it’s unsafe to use Levitra and alcohol together. If you’re still concerned about using them together, try taking Levitra without alcohol the first few times you use it. This will help you figure out if the drug works well on its own.
Would a different ED medication work better for me?Could alcohol use be causing my ED problems?What symptoms should I watch for if I drink alcohol while taking Levitra?Are there natural options that might help relieve my ED symptoms?
Learn more about Levitra: Dosage, use, side effects, and more »
Contents
- 1 Is it OK to take sildenafil with alcohol?
- 2 Can I take tadalafil 20 mg after alcohol?
- 3 Can you take tadalafil or sildenafil with alcohol?
- 4 Can I have a glass of wine with sildenafil?
- 5 How many drinks can you have with sildenafil?
- 6 Can I drink on tadalafil?
- 7 What happens if you mix tadalafil and alcohol?
- 8 Does sildenafil make you harder than tadalafil?
- 9 Does caffeine affect sildenafil?
- 10 Can you crush up Viagra and put it in a drink?
- 11 How can I enhance the effects of Viagra?
Does Cialis still work with alcohol?
FAQs – Does Alcohol Affect Cialis? A little alcohol is not likely to affect the efficacy of Cialis. For example, if you’re planning to have a drink or two with dinner while using Cialis, you aren’t likely to experience serious interactions between the medication and alcohol.
However, this doesn’t mean you shouldn’t be mindful of how much alcohol you consume when using Cialis. The manufacturer of Cialis indicates that drinking five or more alcoholic beverages, with one beverage defined as a glass of wine, beer, or a shot of spirits, can increase your chances of experiencing low blood pressure, a racing heart, or dizziness.
To treat erectile dysfunction, an effect of Cialis is the widening of blood vessels that allow blood to flow to the penis. Wider blood vessels result in lowered blood pressure. Since alcohol can also lower blood pressure, excessive drinking while using Cialis can potentially result in worryingly low blood pressure and dizziness.
- Additionally, excessive drinking is associated with erectile dysfunction, which is the very problem that Cialis is taken to treat.
- Limiting alcohol consumption while using Cialis is generally a good idea, but moderate consumption is safe and unlikely to result in interactions.
- Does Cialis Work? Yes, Cialis works to treat erectile dysfunction.
Cialis is a very effective and widely used treatment for erectile dysfunction, affecting nearly half of Canadian men over 40. Erectile dysfunction is a persistent and recurring inability to get an erection that is firm enough or long-lasting enough for satisfying sexual activity.
- This can be a frustrating experience for the millions of men who experience it.
- Still, effective medications for ED, such as Cialis, make it possible to resume an everyday, satisfying sex life.
- Cialis belongs to a class of drugs called DPE5 inhibitors, making blood flow to the penis easier.
- Since this blood flow is necessary for an erection to be achieved and maintained, Cialis can help in cases of ED in which a person has difficulty getting an erection and cases in which they can get an erection but have trouble maintaining it.
Different doses of Cialis are available, and a licensed healthcare practitioner can help you determine which dose is right for you. There is also a daily version available, which some people prefer the freedom to be spontaneous that it allows for. How Safe Is Cialis? Cialis is generally a very safe and well-tolerated medication for erectile dysfunction.
- Cialis and other generic versions of the same drug, called tadalafil, have been used for over 20 years to treat erectile dysfunction.
- It is among the most commonly prescribed treatments for this condition, and since close to half of Canadian men over 40 experience erectile dysfunction sometimes, it is widely used.
However, Cialis is a prescription medication with some contraindications and side effects. It isn’t available over the counter, and a healthcare practitioner will assess your situation and other medications you may be taking to determine if Cialis is right for you.
Cialis has some contraindications, including organic nitrates used to treat chest pain. Some medical conditions are not compatible with taking Cialis. In these cases, a doctor won’t prescribe Cialis. Another consideration when taking Cialis is to be mindful of alcohol consumption. While you can safely consume Cialis and alcohol together, alcohol should be limited.
The manufacturer indicates that five or more beverages consumed while taking Cialis can increase the risk of experiencing side effects such as dizziness and low blood pressure. How Does Cialis Work? Cialis works by relaxing blood vessels, making blood flow to the penis tissue easier, and enabling it to become erect.
- It belongs to a class of PDE5 inhibitors, which block an enzyme that regulates blood flow to the penis and other tissues.
- Cialis, like other PDE5 inhibitors, make it easier for blood to flow to the penis so that an erection can be achieved and maintained.
- Cialis is usually taken about 30 minutes before sexual activity, and it can remain effective for up to 36 hours in some users, but its effectiveness will taper off over time.
It’s worth noting that you still have to be sexually aroused for Cialis to work. Cialis does not produce an erection without arousal or stimulation. In other words, you don’t have to worry about getting an unwanted erection at the wrong time due to taking Cialis.
Priapism is a rare condition in which an erection occurs and lasts more than four hours. This is considered a medical emergency, and seeking medical attention is necessary. However, most people who use Cialis will never experience this side effect. Can Cialis Be Taken With Alcohol? Yes, you can take Cialis with alcohol.
Consuming moderate alcohol while taking Cialis is generally safe and will not cause interactions with the medication. However, excessive consumption of alcohol is associated with symptoms of erectile dysfunction. Having more than a few drinks while taking Cialis can be counterproductive.
- Additionally, the medication manufacturer advises against having five or more drinks while taking Cialis due to the increased risk of side effects such as dizziness and low blood pressure.
- This doesn’t mean that alcohol has to be avoided altogether when taking Cialis, but it is best to keep your alcohol consumption to one or two drinks when you’re planning to use this medication.
Whether taking Cialis with alcohol or on its own, it’s essential to be aware of the side effects so that you can take action if you experience them. These include dizziness, lightheadedness, headache, flushing, nausea, and runny nose.
Is it OK to take sildenafil with alcohol?
There are 2 alcohol/food/lifestyle interactions with sildenafil. Sildenafil can lower blood pressure, and combining it with ethanol may further increase this effect. You may be more likely to experience symptoms such as dizziness, lightheadedness, fainting, flushing, headache, and heart palpitations.
- You should avoid or limit the use of alcohol while being treated with sildenafil, and use caution when getting up from a sitting or lying position.
- It is important to tell your doctor about all other medications you use, including vitamins and herbs.
- Do not stop using any medications without first talking to your doctor.
Switch to professional interaction data If you are receiving therapy with sildenafil you should avoid the regular consumption of large amounts of grapefruits and grapefruit juice. Grapefruit can raise the levels of sildenafil in your body and delay the time it takes for the medication to work.
Does alcohol affect ED treatment?
The lowdown – Depending on how much you drink, alcohol could be helpful or harmful to erectile dysfunction. However, alcohol has minimal usefulness in treating ED. It’s likely that alcohol, when consumed in moderate amounts, only has the potential to help you manage the psychological causes of the condition, not the physical ones.
- On the other hand, binge drinking or chronic consumption of excessive amounts of alcohol on any specific occasion is unsafe and can lead to the development of alcohol-induced ED.
- This condition is quite common in men after a big night but may be an indication of an unhealthy lifestyle if it happens repeatedly.
Alcohol has many adverse health effects on the body and can significantly affect your mental and social well-being. If you drink alcohol and are concerned about the impact drinking has on your life, speak with your doctor.
Can I take tadalafil 20 mg after alcohol?
Hypotension – Large amounts of alcohol whilst on tadalafil or Cialis, increases your risk of orthostatic hypotension –dizziness or light-headedness that comes about when you stand up. Sudden drops of blood pressure can cause you to faint, or black out.
Can you take tadalafil or sildenafil with alcohol?
How does sildenafil work? Sildenafil belongs to a group of medicines called phosphodiesterase 5 (PDE5) inhibitors. It works if you have erection problems by temporarily increasing blood flow to your penis when you get sexually excited. It works in pulmonary hypertension by relaxing blood vessels in your chest.
you have not waited long enough after taking it before trying to have sexyou have waited too long after taking it to have sexthe dose is not high enoughyou’re not sexually aroused
Are there any long-term side effects? Sildenafil is safe to take for a long time. There do not seem to be any lasting harmful effects from taking it for many months and years. How does it compare to other medicines that can treat erection problems? If sildenafil does not work, there are other tablets you could try that work in a similar way, such as:
tadalafil (Cialis) – can be taken up to 36 hours before sexavanafil (Spedra) – can be taken up to around 4 hours before sexvardenafil (Levitra) – can be taken up to around 4 hours before sex
You could also try a medicine called alprostadil. This is a synthetic hormone that helps to stimulate blood flow to the penis. Alprostadil comes as:
an injection directly into your penisa small pellet placed inside your urethra (the tube that carries pee from your bladder to the tip of your penis)
If you cannot get erections because of a hormonal problem, your GP may refer you to an endocrinologist (who specialises in the treatment of hormonal problems). You may benefit from treatment using injections of synthetic hormones to restore your hormone levels to normal. Are there other treatments for erectile dysfunction? Other treatments for erectile dysfunction include:
a vacuum pumppsychological treatmentspenile implantspelvic floor muscle exercises
Is there a herbal Viagra? There are lots of treatments that claim to be a “herbal Viagra”. In fact, there’s no such thing. A herbal Viagra has never been approved as a treatment for erectile dysfunction. Plus, these treatments may be fake or unsafe. Can women use it? Women can take sildenafil for pulmonary hypertension.
There’s no good evidence that sildenafil works for women with sexual problems. Will it affect my contraception? Sildenafil does not affect any type of contraception, including the combined pill or emergency contraception, Can I drive or ride a bike? Sildenafil does not make you sleepy and so it’s usually safe to drive or ride a bike while taking this medicine.
However, do not drive, cycle or operate machinery if it makes you feel dizzy or affects your eyesight. Can I drink alcohol while taking sildenafil? Yes, you can drink alcohol while taking sildenafil. But drinking lots of alcohol can make it more difficult to get an erection.
To get the most benefit from sildenafil if you’re taking it for erection problems, do not drink much alcohol before taking it. Is there any food or drink I need to avoid? Do not drink grapefruit juice if you’re taking sildenafil (Revatio) for pulmonary hypertension. It affects the way the medicine works.
You can eat and drink normally while taking sildenafil to get an erection. Will recreational drugs affect it? Taking poppers (amyl nitrite) with sildenafil can have a dangerous effect on your heart. It can also be dangerous to take sildenafil with:
stimulants like MDMA (ecstasy) or cocainehallucinogens like LSDnovel psychoactive substances (which used to be known as legal highs) like mephedrone
Sildenafil has not been properly tested with recreational drugs. Talk to your doctor if you think you might use any recreational drugs with sildenafil. You can find out about the side effects of recreational drugs on the Frank website, Can lifestyle changes help with erection problems? Erection problems ( erectile dysfunction ) can often get better if you make changes to your lifestyle, such as:
maintaining a healthy weight quitting smokingcutting down on the amount of alcohol you drinknot taking recreational drugsexercisingreducing stress
Page last reviewed: 2 March 2022 Next review due: 2 March 2025
Can I have a glass of wine with sildenafil?
Sildenafil citrate (brand name: Viagra) is used to treat erectile dysfunction, a health condition that leads to difficulty getting and maintaining an erection. Mixing Viagra with alcohol is probably okay if you’re generally healthy otherwise, granted that it’s only one or two drinks.
- However, unknown to a lot of people, many factors can intensify the side effects of both alcohol and Viagra; for example, other medications and supplements that you’re currently taking, age, and other health problems are some of the contributing factors.
- So even though it is common to have a drink to feel relaxed before sex, it is best to consult your healthcare provider to avoid undesirable or even harmful adverse effects.
Please keep reading to learn more about the potential dangers of mixing alcohol and Viagra.
How many drinks can you have with sildenafil?
How much sildenafil and alcohol is too much? – If you are going to consume alcohol while taking Viagra, be sure to do so responsibly. Limit your alcohol intake to 1–2 drinks per day. According to the Centers for Disease Control and Prevention (CDC), the amount of alcohol in a standard drink is one of the following ( CDC, 2020 ):
- 12 ounces of beer (5% alcohol content)
- 8 ounces of malt liquor (7% alcohol content)
- 5 ounces of wine (12% alcohol content)
- 1.5 ounces or a “shot” of 80-proof (40% alcohol content) distilled spirits or liquor (e.g., gin, rum, vodka, whiskey)
Drink water or nonalcoholic beverages in between the alcoholic drinks to prevent dehydration. Know your limits, and be sure to stop drinking alcohol when you start to feel intoxicated. And, for those on certain prescription drugs like nitrates or alpha-blockers, do not take Viagra, even without alcohol, before speaking with your healthcare provider as negative drug interactions and serious side effects can occur when these are combined with Viagra.
What can I take to enhance Cialis?
How Does Grapefruit Affect Cialis? – Let’s put it like this, if you were thinking of washing your dose of Cialis down with a glass of grapefruit juice, maybe swap it for a glass of water or orange juice. According to a study published in the American Journal of Cardiovascular Drugs, grapefruit juice can cause a drug interaction when taken with certain drugs, and Cialis is one of them.
- To explain, a drug interaction occurs when the effects of a medication are altered when another substance is taken.
- These effects may enhance the benefits or reduce the effectiveness of the drug.
- In some cases, it may cause toxicity.
- In the case of grapefruit and Cialis, this liquid or the fruit itself produces an unwanted effect.
In its role as a PDE-5 inhibitor, tadalafil acts as a vasodilator to promote the flow of blood to the penis. When combined with grapefruit, this effect can cause a serious increase in blood flow around the body, especially when combined with nitrates.
This is because grapefruit can increase the amount of Cialis in your body. It can achieve this by preventing presystemic metabolism — a process where the concentration of Cialis is reduced before it reaches circulation in the body. CYP 3A4 (an enzyme in your intestine) is responsible for this metabolism.
When inhibited by grapefruit, there can be higher amounts of Cialis in the body. But this effect isn’t limited to just Cialis. Grapefruit has been known to cause similar effects when taken with antihypertensives, as well as other PDE5 inhibitors like sildenafil (generic Viagra) and vardenafil.
Why can’t I get hard after drinking alcohol?
Short-term causes of ED – A temporary inability to get an erection can happen after consuming any type of alcohol. According to a 2018 study, short-term consumption of alcohol depresses your central nervous system and slows down the transmission of information between your brain and penis.
- This can lead to decreased sensitivity of the penis.
- Alcohol is a diuretic, meaning it’s dehydrating and increases urination.
- Dehydration can lead to increased levels of the hormone angiotensin, which narrows blood vessels.
- Angiotensin can limit blood flow to the penis.
- According to older 1998 research and more recent animal studies, alcohol can also lead to a drop in circulating levels of testosterone.
Testosterone deficiency limits nitric oxide production, which is the key molecule that relaxes the blood vessels in your penis.
How many beers can you have with Viagra?
No alcohol with Viagra? – It is important that you limit your alcohol intake while you are taking Viagra but it is safe to enjoy a small amount of alcohol, such as 2 – 3 units – so there’s is nothing wrong with having a glass of wine or one beer.
Can alcohol cause ED even when sober?
Nothing can put a damper on an amorous mood faster than a case of alcohol-related erectile dysfunction (ED), also known in more vulgar terms as “whiskey dick.” While you and your partner may be excited to parlay your margarita buzz into an evening of sex, there could be times when your penis won’t rise to the occasion.
- Alcohol and sex have a complicated relationship.
- According to a recent study on behavior-related erectile dysfunction in the Journal of Sexual Medicine, when alcohol is consumed in moderation (1 to 2 drinks a day), it is shown to increase desire and reduce anxiety about sexual performance, both of which are beneficial to ED.
However, when it is consumed in excess, alcohol can have quite the opposite effect. The following is a closer look at the association between alcohol and erectile dysfunction. What is it? Alcohol-induced erectile dysfunction is a temporary condition due to overindulging in alcohol.
- This could refer to the inability to achieve an erection at all or a situation in which a person gets an erection that is weaker or shorter-lasting than desired.
- Why does it occur? Because erectile dysfunction is usually the result of multiple factors, it can be difficult to isolate one variable from the rest to study it.
However, researchers generally agree that excessive alcohol consumption affects male sexual function in the following ways:
As a depressant, alcohol has a slowing effect on the activity of the Central Nervous System (CNS). The CNS is made up of the brain and spinal cord, and it is responsible for bringing in information from the senses and relaying information to the rest of the body. When the CNS is depressed by alcohol, thinking and reasoning are impaired, reaction times slow, and motor skills and coordination suffer. Unfortunately, the signals between the brain and penis are not immune to the slowing effect of alcohol, sometimes resulting in ED when a man drinks too much. Alcohol is a diuretic, meaning that it causes a person to urinate more frequently than usual and can result in dehydration. Dehydration decreases the volume of blood in the body, also decreasing blood flow to the penis and making it more difficult to get an erection. Lastly, dehydration increases the body’s level of angiotensin, which is a hormone associated with erectile dysfunction.
Are certain types of alcohol more likely to cause it? As far as we know, no. Any type of alcohol can cause the symptoms, and it is more likely related to the actual amount of alcohol present rather than the alcohol itself. What should I do if it happens to me? First of all, relax and know that it could happen to anyone who indulges in alcohol from time to time.
Open, honest communication with your partner is the best policy (as in most situations related to sexual dysfunction), but if you prefer not to have this conversation, you can always partake in other sexual/sensual activities that do not require an erection, like oral sex, petting, or massages. If it happens to your partner, the advice is similar.
Recognize that alcohol-related ED is common, and it is not a reflection of your partner’s feelings for or attraction to you. Try not to make a big deal out of it and enjoy other activities with your partner if you are both so inclined. When does it become more serious? An occasional case of alcohol-induced ED is nothing to fret about, but if you repeatedly find yourself unable to achieve an erection, even while sober or after drinking a small amount of alcohol, you could benefit from speaking with your doctor about your situation.
Additionally, if you worry that your alcohol consumption may be excessive or out of your control, seek counselling from a medical professional. Resources American Addiction Centers Editorial Staff. (2020, November 3). Is Alcohol Wreaking Havoc on Your Sexual Performance? DrugAbuse.com. https://drugabuse.com/blog/is-alcohol-wreaking-havoc-on-your-sexual-performance/ Jewell, T.
Medically reviewed by Deborah Weatherspoon, Ph.D., R.N., CRNA. (2019, May 23). Does Alcohol Dehydrate You? Healthline. https://www.healthline.com/health/does-alcohol-dehydrate-you/ Martin, M. Medically reviewed by Dr. Mike Bohl, MD, MPH. (2020, May 15). “Whiskey Dick” or alcohol-induced erectile dysfunction.
- Roman. https://www.getroman.com/health-guide/whiskey-dick-erectile-dysfunction/ Santos-Longhurst, A.
- Medically reviewed by Janet Brito, Ph.D., LCSW, CST.
- 2019, October 29).14 FAQs About “Whiskey Dick.” Healthline.
- Https://www.healthline.com/health/healthy-sex/whiskey-dick Sivaratnam, L., Selimin, D.S., Abd Ghani, S.R., Nawi, H.M., Nawi, A.M.
(2021). Behavior-Related Erectile Dysfunction: A Systematic Review and Meta-Analysis. The Journal of Sexual Medicine, 18 (1), 121-143. https://www.jsm.jsexmed.org/article/S1743-6095(20)30930-9/fulltext
Can I drink on tadalafil?
There is 1 alcohol/food/lifestyle interaction with tadalafil. Tadalafil can lower blood pressure, and combining it with alcohol may further increase this effect. You may be more likely to experience symptoms such as dizziness, lightheadedness, fainting, flushing, headache, and heart palpitations.
- You should avoid or limit the use of alcohol while being treated with tadalafil, and use caution when getting up from a sitting or lying position.
- You may also want to avoid drinking large amounts of grapefruit juice, since it may increase the blood levels and effects of tadalafil.
- It is important to tell your doctor about all other medications you use, including vitamins and herbs.
Do not stop using any medications without first talking to your doctor. Switch to professional interaction data
How long can you stay hard with tadalafil?
How Long Does Tadalafil Last? – We’d like to give you a short answer to this seemingly simple question, but we can’t yet. How long tadalafil lasts is a hard question to answer, as it depends on two factors: dosage and usage. Generally, tadalafil differs from other FDA-approved PDE5 inhibitors offered at pharmacies in that it has a significantly larger time frame of efficacy.
- Once daily at a dose between 2.5 and 5-mg tablets
- As needed at a dose between 5 and 20-mg tablets
In both cases, it’s possible Cialis will last for up to 36 hours. But you should never take Cialis more than once daily, as it may last the full 36 hours. That’s not to say you’ll be erect for 36 hours. First, that would be very dangerous for your penis, and second, it would have probably stopped being fun somewhere around the 32-hour mark.
Many men might argue there’s no such thing as a “too long” erection. But these guys haven’t heeded the warnings of erections lasting more than four hours — a condition called priapism. Priapism is arare side effect of ED drugs that results in prolonged erections, which can damage blood vessels and potentially permanently damage your member.
Erections lasting more than four hours sound kind of painful — if you have one, seek emergency medical attention.
Why is tadalafil not working?
Common questions about tadalafil Other medicines are usually taken on demand, 30 to 60 minutes before sexual activity. The alternatives to tadalafil work for up to 4 hours. If you take tadalafil, it can be effective for up to 36 hours. If tadalafil does not work, there are other tablets you could try that work in a similar way, such as:
sildenafil (Viagra)avanafil (Spedra)vardenafil (Levitra)
Only is available without prescription. You can take tadalafil and vardenafil with or without food. However, it’s best to take sildenafil and avanafil on an empty stomach for fastest effects. Eating a meal that is high in fat may delay the effect of vardenafil.
an injection directly into your penisa small pellet placed inside your urethra (the tube that carries pee from your bladder to the tip of your penis)
If you cannot get erections because of a hormonal problem, your doctor may refer you to an endocrinologist (a doctor who specialises in the treatment of hormonal problems). They may recommend hormone injections to bring your body’s levels back to normal. : Common questions about tadalafil
What happens if you mix tadalafil and alcohol?
The effects of combining tadalafil and alcohol – Now that you’re aware that it’s safe to have a drink or two when you’re taking Cialis let’s talk about what happens to the body if your alcohol consumption is higher than the recommended limit while you’re on Cialis.
- First, it’s good to remember that both alcohol and Cialis lower your blood pressure, so combining them can increase that effect, sometimes dangerously.
- Low blood pressure can lead to dizziness, headaches, and rapid heartbeats.
- In extreme cases, it can make you lose consciousness (Eli Lilly, 2008; Kim, 2019 ).
Then, there’s the unwanted risk of ” whiskey dick,” You’ve probably heard, or experienced firsthand, that alcohol makes it harder to get an erection ( Arackal, 2007 ). If you struggle with erectile dysfunction, steering clear of alcoholic beverages may be a good idea.
Does sildenafil make you harder than tadalafil?
Cialis vs Viagra: which gets you harder? – Contrary to popular belief, neither erectile dysfunction medication, Cialis or Viagra, is able to make you harder than the other. Each ED treatment is effective at helping men achieve and sustain an erection during sex. Buy Cialis Tablets – ED Treatment Cialis Tablets are available to buy online when you complete an online consultation. In just a few simple steps get ED treatment delivered directly to you. View Treatment
Which is better Levitra or Cialis?
Are there reasons why Cialis is a better treatment option than Levitra or vice versa? – Yes, certain factors could make one drug a better treatment option than the other. For example, Cialis may work faster than Levitra for treating erectile dysfunction (ED),
For this reason, Cialis can be taken about 30 minutes before sexual activity, while Levitra should be taken about 1 hour beforehand. Cialis is also approved for daily use, while Levitra is not. This means Cialis can be taken once daily at the same time each day, regardless of the timing of sexual activity.
Levitra is typically taken only as needed before sexual activity. In addition to ED, Cialis is approved to treat the symptoms of a prostate condition called benign prostatic hyperplasia (BPH), If you have both ED and BPH, Cialis may be a better treatment option for you than Levitra.
This is because Cialis can be used to treat both ED and BPH symptoms, while Levitra is only approved to treat ED. The manufacturers of Cialis and Levitra have not provided reviews from people who have taken either drug. If you have questions about how Cialis compares with Levitra, talk with your doctor or pharmacist.
Note: For more information about the dosages for Cialis, see this article, To learn more about the uses for Cialis, see this article, You can also refer to the prescribing information for Cialis and Levitra,
Does caffeine affect sildenafil?
Influence of Energy Drinks on Pharmacokinetic Parameters of Sildenafil in Rats Abdulla M, Mallah E, Dayyih W. A, Rayyan W. A, El-Hajji F. D, Bustami M, Mansour K, Al-Ani I, Seder N, Arafat T. Influence of Energy Drinks on Pharmacokinetic Parameters of Sildenafil in Rats. Views: (Visited 31,794 times, 1 visits today) PDF Downloads: 794
- Mohammad Abdulla 1, Eyad Mallah 1, Wael Abu Dayyih 1, Walid Abu Rayyan 1, Feras Darwish El-Hajji 2, Mona Bustami 1, Kenza Mansour 1, Israa Al-Ani 3, Nisreen Seder 4 and Tawfiq Arafat 1
- 1 Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.
- 2 Faculty of Pharmacy and Medical Sciences, Applied Science University, Amman, Jordan.
- 3 Faculty of Pharmacy and Medical Silences, Al-Ahliyya Amman University, Jordan.
- 4 School of Biomedical Science, Faculty of Health Sciences, University Sultan Zainal Abidin, 21300 Kuala Nerus, Terengganu, Malaysia.
- Corresponding Author E-mail:
- DOI :
- Abstract
Both sildenafil and RED BULL ® (energy drink) are claimed to boost up energy.RED BULL ®, one of the most commonly used energy drinks and its easily and widely available for daily use, the idea of this research work had arisen from observations about the concomitant use of sildenafil with RED BULL ® by men seeking for better sexual performance. To study the effect of RED BULL ® on the pharmacokinetic profile of sildenafil by using HPLC.The pharmacokinetic parameters (C max, T max and AUC) were determined in 10 rats following oral administration of 0.57 mg/ml sildenafil with and without RED BULL ® in crossover design, to achieve this purpose,simple, rapid and accurate method for validation and determination of sildenafil in rat plasma in the presence of RED BULL ® has been developed. This was performed using High-Performance Liquid Chromatography- Ultra Violet (HPLC-UV). The pharmacokinetic data showed that sildenafil plasma level was lower when combined with RED BULL ® According to the results obtained, maximum concentration (C max ) for sildenafil alone was (162.05 ng/ml) after 0.5 hours of administration. The C max decreased to (44.68 ng/ml) after 0.5 hoursof administration RED BULL ® concomitantly with sildenafil which showed a significant effect on sildenafil plasma level (P<0.001). The area under the curve (AUC) decreased significantly from (370.53 ng/ml*hr) for sildenafil alone to (87.74 ng/ml*hr) when combined with RED BULL ®, RED BULL ® can alter sildenafil pharmacokinetic if they were taken together. Keywords Drug Interaction; Energy Drinks; Pharmacokinetic; Sildenafil; Validation Download this article as:
Copy the following to cite this article: Abdulla M, Mallah E, Dayyih W. A, Rayyan W. A, El-Hajji F. D, Bustami M, Mansour K, Al-Ani I, Seder N, Arafat T. Influence of Energy Drinks on Pharmacokinetic Parameters of Sildenafil in Rats. Biomed Pharmacol J 2018;11(3). |
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Introduction Sildenafil citrate is an oral drug used as a therapy for erectile dysfunction.1 It is designated chemically as 1- pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate.2 Sildenafil citrate structure is shown in figure 1.
Figure 1: sildenafil citrate structure, |
The mechanism of erection involves therelease of nitric oxide (NO) in the Corpus cavernosum during sexual stimulation. The NO activates the enzyme guanylatecyclase, which increases the levels of cyclicguanosine monophosphate (cGMP).3 The production of cGMP leads to relaxation of smooth muscles in the corpus cavernosum and increases blood flow into the penis.4 Sildenafil citrate has no direct relaxant effect, but it increases the levels of cGMP by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP.5 Sildenafil is primarily metabolized by the CYP3A4 enzyme, which is the principal enzyme responsible for the oxidative metabolism of themajority ofdrugs.6 The interaction between sildenafil and other drugs that are also metabolized by CYP3A4 should be taken into consideration when drugs are prescribed to avoid undesired pharmacological effects.6-8 RED BULL ® is the best-selling energy drink in theUnited States of America and worldwide.
It contains different ingredients such as sugar, caffeine, taurine, glucuronolactone and B vitamins.9 Caffeine is probably the most common ingredient in RED BULL ®, as it acts as a stimulant.10 Taurine is a homocysteine derived amino acid, but not a constituent of proteins.11 It is present freely in the intracellular fluid and distributed widely in the sarcoplasm of the cardiac tissues, hepatocytes, central nervous system, and retina.
Taurine mediates the homeostasis of different physiological functions 12 including osmoregulation,antioxidation,detoxification, neuromodulation, and brain and retinal development.13 Moreover, a number of studies have documented some pharmacological functions of taurine against congestive heart failure, liver disease, hyperlipidemia.14 Several papers reported that Sildenafil pharmacokinetics are altered in response to food-drug (or drug-drug)interactions.5, 15-17 It has been demonstrated the co-administration of sildenafil with potent CYP3A4 inhibitors such as azole antifungal agents, macrolide antibiotics, and protease inhibitorscauses a significant increase in plasma sildenafil levels.18, 19 Another example of interaction is Sitaxentan (endothelin receptor antagonist), which when administered with sildenafil, demonstrated a weak, but a statistically significant interaction.20 The effect of concomitant administration of caffeine with certain drugs used for cardiovascular, CNS, gastrointestinal, infectious, respiratory and skin disorders has been extensively studied as well.21 whereas, the effect of other ingredients in Red Bullhas not been studied for the pharmaco kinetic effect on sildenafil.
Caffeine has been reported to interact with many medications such as certain selective serotonin reuptake inhibitors (particularly fluvoxamine), antiarrhythmics (mexiletine), antipsychotics (clozapine), psoralens, idrocilamide and phenylpropanol amine, quinolones (enoxacin) and bronchodilators (furafylline and theophylline).10 Thus, pharmaco kinetic interactions at the CYP1A2 enzyme level may cause toxic effects during concomitant administration of caffeine and certain drugs used for cardiovascular, CNS, gastrointestinal, infectious, respiratory and skin disorders.9 Recently, drug-drug and drug-food interactions are being the center of our interest.22-26 The idea of this research work had arisen from observations of about the concomitant use of sildenafil with RED BULL ® by men seeking for better aphrodisiac effect during sexual intercourse.
Both Sildenafil and RED BULL ® claimed to boost up energy.Since RED BULL ® is one of the most commonly used energy drinks, it is easily and widely available for daily use. The current study was conducted to investigate the effect of RED BULL ® ingestion on the pharmacokinetics of Sildenafil in rats plasmausing HPLC in a crossover study.
- Materials and Methods
- Reagents and Materials
- Deionized Water, Nano pure (Fischer Scientific), Rats plasma (from animal house in ASU)
- Methanol, advanced gradient grade (Fischer scientific),Acetonitrile (ACN) (Fisher), Triethylamine (TEDIA), Phosphoric acid (Medex), Sildenafil (from Dar al-Dawapharma),
- Carbamazepine, EDTA, Distilled water.
- Instrumentation
An HPLC (FinniganSurveyor) was used and composed ofChromQuestsoftware 4.2.34, Solvent delivery systems pump (LC Pump Plus), Auto-sampler plus, UV-VIS plus Detector, Sepax GP-C18, (150 x 4.6 mm), 5µm.
Figure 3: Mean plasma sildenafil concentration in female rats with time after drug administration, compared to its combination with RED BULL ®, |
Each data point represents the mean (n=10). Preclinical Study and Protocol Adult female Sprague-Dawley laboratory rats were supplied by the animal house of Applied Science University. The average weight of these rats was about 240g (200g -260), and they were in healthy condition.
- They were placed in anair-conditioned environment (20-25°C) and were exposed to 12 hours light/12 hours dark cycle daily.
- All animals in the experiments were handled in compliance with FELASA guidelines (Federation of European Laboratory Animal Science Association) and the study protocol was approved by the research committee (February 2014) at the Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan.10 rats were included in the drug interaction study in a crossoverstudy.The rats were divided into 2 groups (group A and group B), 5 rats each.In the first period of the experiment, group (A) had received sildenafil aqueous solution with a concentration of 0.57 mg/ml and a dose of 2.85/kg (200mg/70kg)alone as a single dose, while group (B) had received sildenafil aqueous solution as a single dose with RED BULL ® (purchased from local market), respectively and spontaneously.
Washing out period of2 weeks was implemented, after which the test items were switched between the 2 groups, Group (A) received sildenafil solution and RED BULL ® while group (B) received sildenafil solutionalone. The dose used is corresponding to 200 mg for human of 70 kg weight, 200 mg is the double dose of sildenafil regular dose.
This dose was chosen to clarify any possible interaction, as it foundto be usedin theprevious clinical trial.27 The least weight of rats was 200g and the concentration was calculated based on this weight. Rats weighing200 mg took 1 ml of the solution, and then other rats took more than 1ml according to their weights.
The ratswhich were aimed to take RED BULL ® in each part of the experiment were supplied with 15 ml, 16 hours before sildenafil solution administration. They receivedanother 5ml of RED BULL ® orally after the administration of sildenafil solution. A syringe with a specific needle was used for the oral administration of both sildenafil and RED BULL ® solutions.For rats which were aimed to take sildenafil solution alone, drinking water was administrated insufficient amount all the time.
Blood samples were taken from the rats’ optical vein at the following time points: (zero, 0.5, 1, 1.5, 2.5, 4, 6, 7.5) hours. Blood samples were drawn into EDTA-containingmicrotubes. The microtubeswere immediately centrifuged for 10 minutes at 5,000 rpm and separated plasma was transferred into labeled Eppendorf tubes then stored at -20°C until analysis.
Preparation of Solutions Preparation of Sildenafil Solution for Oraluse 0.081 g of sildenafil citrate (equals to 0.057 g sildenafil) was dissolved in 100 ml of distilled water, vortex to have complete dissolution to get a concentration of 0.57 mg/ml.
- Preparation of Stock Solution of Sildenafil
- An equivalent weight of 10mg of sildenafil working standard was dissolved in 10 ml of methanol to getaconcentration of 1000 µg/ml stock solution of sildenafil.
- Preparation of Stock Solution of Carbamazepine Internal Standard
- An equivalent weight of 10 mg of carbamazepine working standard was dissolved in 100 ml of Acetonitrile to get a concentration of 100 µg/ml stock solution of carbamazepine.
- Preparation of Working Solution of Carbamazepine I.S
20 µl were taken from carbamazepine stock solution (100µg/ml) and diluted to 100 ml using ACN which was considered to be anI.S working solution that contains 20 ng/ml of carbamazepine. Method of Extraction Thedescribed procedures were applied for subject samples, calibrator, and quality control samples.
In order to perform the sample extraction, disposable Eppendorf tubes were labeled and placedon a rack, then 100.0 µl aliquots of each test sample (blank, zero, standards, quality control low, quality control medium, quality control highand rat samples) were drawn into the tubes by pipette and mixed with 150.0 µl of internal standard (20 ng/ml carbamazepine in ACN), then vortex of each sample vigorously for 1.0 min, and finally Centrifugation at 14000 rpm for 15 minutes.
Chromatographic conditions and detection conditions were as follow in table I: Table 1 : Chromatographic conditions and detection conditions.
Column Oven Temp | Auto-sampler Temp | Auto-sampler Injection Volume | Pump Flow Rate | HPLC Conditions |
30˚C | 10˚C | 25 µl | 1.0 ml/ min | |
Mixture of (57.5 % ACN, 42.5 Water), 675 µl Triethylamine /1L of mixture, pH=7.0 adjust pH with phosphoric acid | Mobile phase | Chromatography | ||
Sepax GP-C18, (150 x 4.6 mm, 5µm) | Column type | |||
Sildenafil | Carbamazepine(I.S) | Expected Retention times (minutes) | ||
4.2 min | 2.5 min | |||
230 nm | Wavelength | Detection Conditions |
Analytical Method Validation Accuracy and Precision The intra-day precision and accuracy were evaluated by analyzing six replicates of the QC samples (low, mid, high) and lower limit of quantification (LLOQ) samples on a single day. The inter-day precision and accuracy were determined by analyzing three runs of QC samples and LLOQ samples on three different days.
The accuracy (%) was calculated by dividing a measured mean concentration over the nominal analyte concentration. Precision was presented as CV%. The acceptable limits of accuracy and precision should be below 15% except at the LLOQ, for which accuracy and precision should be below 20%.28 Linearity Linearity was determined by a series of six injections to a seven calibration concentration levels for theanalyte.
Peak areas of the calibration standards were plotted in the Y-axis against the nominal standard concentration, and the linearity of the plotted curve was evaluated through the value of the correlation coefficient (R2) which should be more than 0.98.28 Stability Stability of the analyte in the rat serum was evaluated using both low and high QC samples, which were analyzed immediately after preparation and after the applied storage conditions.Evaluation included:autosampler stability, freeze-thaw stability “after 3 cycles”, and Short-term stability at room temperature “24 h”.
- The mean concentration should be within ±15% of the nominal concentration.28
- Results and Discussion
- Validation
The validation of sildenafil was conducted according to EMA guideline.28 Selected chromatograms for sildenafil validation (blank, zero, LLOQ) are shown in figures (4, 5 and 6).
Figure 4: Sildenafil blank chromatogram. |
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Accuracy and Precision Table IIrepresents inter-dayprecision and accuracy for quality control samples of sildenafil in three days of validation. All of the obtained accuracy and precision data were within the required range which is (85-115 % for all concentration except forLLOQ, which is 80-120 %) for the accuracy, and (20 % for LLOQ and 15 % for other concentrations) for the precision.
Conc./Days | 20 ng/ml | 60 ng/ml | 250 ng/ml | 425 ng/ml |
Mean (n=6) | 20.398 | 60.535 | 257.891 | 426.620 |
STD | 1.324 | 2.436 | 6.425 | 7.376 |
CV% | 6.492 | 4.023 | 2.491 | 1.729 |
Accuracy% | 101.99 | 100.89 | 103.16 | 100.38 |
Linearity R 2 which represents the strength of correlation coefficient for standard calibration curve was greater than 0.99 during validation course. Data of standard curve with regards to correlation, slope, R 2, and intercept are shown in tables III.
Correlation | Slope | Factor | R 2 | Intercept |
0.999963 | 0.002158 | 463.45431 | 0.999927 | -0.002794 |
Stability TablesIV shows data for short-term stability indicated by two QC concentrations (low, high) for sildenafil after preparation procedure (auto-sampler stability), T=10°C and for room temperature or processing temperature. Regarding to the stability of plasma samples during freezing and thawing processes; two QC samples were stored and frozen in afreezerat the intended temperature-60°Cand thereafter thawed and processed at room temperature twice for 72 hours.All results were within the accepted range of 85%-l 15%.
Sildenafil QC low samples stability auto-sampler procedure at 10°C. | Sildenafil QC high samples stability auto-sampler procedure at 10°C. | ||||||||
Time | Measured Conc. | Mean Measured | Accuracy % | Stability | Time | Measured Conc. | Mean Measured | Accuracy % | Stability |
0.00 Hour | 61.959 | 61.195 | 103.27 | 100.00 | 0.00 Hour | 427.436 | 426.263 | 100.57 | 100.00 |
60.624 | 101.04 | 423.162 | 99.57 | ||||||
61.002 | 101.67 | 428.190 | 100.75 | ||||||
24.00 Hours | 59.474 | 59.902 | 99.12 | 97.89 | 24.00 Hours | 426.317 | 423.081 | 100.31 | 99.25 |
60.462 | 100.77 | 424.062 | 99.78 | ||||||
59.771 | 99.62 | 418.864 | 98.56 | ||||||
Sildenafil QC low samples stability at room temperature (bench stability). | Sildenafil QC high samples stability at room temperature (bench stability). | ||||||||
Time | Measured Conc. | Mean Measured | Accuracy% | Stability | Time | Measured Conc. | Mean Measured | Accuracy% | Stability |
0.00 Hour | 61.959 | 61.195 | 103.27 | 100.00 | 0.00 Hour | 427.436 | 426.263 | 100.57 | 100.00 |
60.624 | 101.04 | 423.162 | 99.57 | ||||||
61.002 | 101.67 | 428.190 | 100.75 | ||||||
24.00 Hours | 59.693 | 58.031 | 99.49 | 94.83 | 24.00 Hours | 426.246 | 422.897 | 100.29 | 99.21 |
57.071 | 95.12 | 420.336 | 98.90 | ||||||
57.329 | 95.55 | 422.109 | 99.32 | ||||||
S ildenafil QC low samples stability at freeze and thaw. | S ildenafil QC high samples stability at freeze and thaw. | ||||||||
Time | Measured Conc. | Mean Measured | Accuracy% | Stability | Time | Measured Conc. | Mean Measured | Accuracy% | Stability |
0.00 Hour | 61.959 | 61.195 | 103.27 | 100.00 | 0.00 Hour | 427.436 | 426.263 | 100.57 | 100.00 |
60.624 | 101.04 | 423.162 | 99.57 | ||||||
61.002 | 101.67 | 428.190 | 100.75 | ||||||
72.00 Hour | 58.712 | 58.871 | 97.85 | 96.20 | 72.00 Hour | 423.093 | 424.899 | 99.55 | 99.68 |
58.713 | 97.86 | 426.925 | 100.45 | ||||||
59.187 | 98.65 | 424.678 | 99.92 |
Pharmacokinetic data of sildenafil in presence of RED BULL ® The plasma concentrations of sildenafil with or without RED BULL ® weremeasured inthe population rats using a sample size of 10 rats for the drug alone and then repeated for the combination of the drug with RED BULL ® in a crossoverstudy with washout period of 2 weeks.7 discrete samples were obtained from rats following drug administration tothelast time interval of 7.5 hours. This study was conducted on female rats since the sildenafil bioavailability is more comparable to humans (regardless the gender) and the plasma levels of sildenafil male rats are much lower when compared to its bioavailability in female rats (16) (17). The plasma levels of sildenafil fed ratshas reached its maximum level at the first 0.5 hours(C max ) (162.05 ng/ml) (T max )when administered alone as depicted in figures (3, 7). Whereas, sildenafil plasma levelswereintimately decreased whenadministered with RED BULL ® as C max was only 44.68 ng/mlatthe first 0.5 hours, as shown in figures(3, 8). The sharp decrease in sildenafil levels as a consequent of administration with RED BULL ® reached a proportion of 72% decrease (P<0.001) compared with sildenafil fed rats alone. Figure 3shows Mean plasma sildenafil concentration of female rats in a crossover study, sildenafil was administered alone and in combination with RED BULL ®,Each data point represents the mean (n=10). The pharmacokinetic interaction of Sildenafil and RED BULL ® could happen at any stage of ADME: "Absorption, Distribution, Metabolism, and Excretion." However, the absorption of sildenafil from the intestine happens through a passive mechanism, no carriers are needed so we rule out this is the cause of the difference.29 The pH of RED BULL ® solutions (with and without Sildenafil) is 3.28, which indicates theminimum effect on stomach pH.In addition, we noted that complete dissolution occurred for Sildenafil in RED BULL®.
Figure 8 : Sildenafil with RED BULL ® sample chromatogram after 0.5 hours of administration for one group. |
However, this cannotrule out the presence of interaction at the absorption level in the stomach as the presence of REDBULL willeffect of the gastric emptying time.26 By plotting the data on thesemilog scale as shown in figure (9), the slope (which represents elimination rate constant) of Sildenafil when administered with RED BULL beverage was steeper, this indicates a higher elimination rate of the drug when combined with RED BULL.
Figure 9: Mean plasma sildenafil concentration in female rats with time after drug administration, compared to its combination with RED BULL ® on asemilog scale. |
Each data point represents the mean (n=10). The lower AUC, Cmaxis accompanied by anincrease in the clearance of the drug and shortening of the half-life. These changes elimination parameters indicate an enhancement in elimination processes of the drug which mainly eliminated by metabolism in theliver.
- By reviewing the literatures, it has been demonstrated that taurine has an activating effect on the expression level of CYP 3A4 in the presence of CYP3A4 inducer.
- Taurine enhances the induction of CYP3A4 mRNA in a concentration-dependent manner.30 Taurine is a potent inducer of CYP3A4 mRNA via pregnane X receptor (PXR), an orphan member of the steroid/retinoid/thyroid hormone receptor superfamily of ligand-activated transcription factors.31, 32 It was recently reported that PXR serves as a functional bile acids receptor, and lithocholic acid, which is a kind of bile acid, induces CYP3A mRNA.33-35 Attention should be paid to drug interactions when taurine-containing medicinal agents, foods, and drinks are administered together with both sildenafil and drugs metabolized mainly by CYP 3A4.35 Moreover,in a similar manner of drug interaction, high levels of taurine have lowered the plasma concentrations of acetaminophen and rifampicine by increasing the enzyme activity of CYP3A4.36, 37 Moreover, we tried to find a single clinical report about overdoseabuse ofsildenafil and REDBULL but up to the date there is no case report about the adverse effect of Sildenafil intake with energy drink.
Our findings couldexplain the reason of why there are no reports on sildenafil interaction with such drinks but even though we don’t know anything about the sildenafil clinical effect since it has reached to a sub therapeutic dose. In addition, we propose that the change in sildenafil plasma levels in female rates is an enzyme induction mechanism due to asignificant change in elimination parameters.
WhereasKelhas been changed significantly from 0.45 hr-1 for sildenafil alone to 0.56 hr-1when given in combination with RED BUL beverage. The terminal elimination t1/2 was shortened significantly from 1.51 hr to 1.15 hr in combination, and the clearance increased also highly significantly from to 135 L/hr/kg to 535.6 L/hr/kg in combination.
Also, the MRT-t was shortened. All these changes suggest an enhancement in elimination processes by metabolism of sildenafil by hepatic enzymes. However, the interaction still could have done at any stage of ADME. Moreover, caffeine has a great impact on the cardiovascular system by causing increased heart rate and blood pressure which results in increased cardiac output.38 So theblood flow to theliver will increase, and the metabolism of sildenafil in presence of caffeine may increase because of this increase in blood flow.
Sildenafil | Sildenafil and RED BULL | |
T-max(hr) | 0.5 | 0.5 |
C-max(ng/ml)* | 162.05 | 44.68 |
AUC(ng/ml*hr)* | 370.53 | 87.74 |
AUMC-t (ng.hr2/ml) | 810.90 | 155.73* |
MRT-t (hr) | 2.18 | 1.66* |
Kel (hr-1) | 0.45 | 0.56* |
T1/2 (hr) | 1.51 | 1.15* |
Systemic Cl (L/hr/kg) | 135 | 535.6* |
All parameters are within a CI of 5%. The difference between both C max and AUC of sildenafil alone and sildenafil withRED BULL ® was statistically significant (P<0.001). Conclusion There is a pharmaco kinetic interaction between sildenafil and RED BULL ® when administrated concomitantly. Such interaction effectssignificantly (P<0.001) the C max and AUC of sildenafil. The interaction between sildenafil and RED BULL ® could happen in all stages with high probability to be executed in metabolism stage. This in vivo trialon rats suggests further investigations,such as assessing the possible interaction between sildenafil and RED BULL ® in humans, checking the pharma cod ynamic effect of this combination, testing sildenafil levels in plasma in presence of certain concentrations of caffeine and explaining the exact mechanism of this interaction and the responsible compounds. Acknowledgment This research was funded by the deanship of scientific research at University of Petra. The technical support from Faculty of Pharmacy and Medical Sciences at University of Petra and the animal house department of Applied Science University was highly appreciated.
- Conflict of Interest
- The authors declare that there is no conflict of interest.
- References
- Berzas J, Rodriguez J, Castaneda G, Villaseñor M. Voltam metric behavior of sildenafil citrate (viagra) using square wave and adsorptive stripping square wave techniques: Determination in pharmaceutical products. Analytica chimica acta,2000;417:143-8.
- Umrani D.N, Goyal R.K. Pharmacology of sildenafil citrate. Indian journal of physiology and pharmacology.1999 ; 43:160-4.
- Moncada S, Higgs A. The l-arginine-nitric oxide pathway. New England Journal of Medicine.1993;329:2002-12.
- Ralph D, McNicholas T. Uk management guidelines for erectile dysfunction. BMJ: British Medical Journal.2000 ; 321:499.
- Cheitlin M.D, Hutter A.M, Brindis R.G, Ganz P, Kaul S, Russell R.O, Zusman R.M, Forrester J.S, Douglas P.S, Faxon D.P. Use of sildenafil (viagra) in patients with cardiovascular disease. Circulation.1999 ; 99:168-77.
- Mallah E.M, Rayyan W.S, Dayyih W.A, Elhajji F.D, Mansour K.A, Al-Majali I.S, Arafat T.A. Dose-dependent synergistic effect of pomegranate juice on the bioavailability of sildenafil in rats by using hplc method. LATIN AMERICAN JOURNAL OF PHARMACY.2016;35:1277-84.
- Krenzelok E.P, Krenzelok E. Sildenafil: Clinical toxicology profile. Journal of Toxicology: Clinical Toxicology.2000;38:645-51.
- Mallah E, Saleh S, Rayyan W.A, Dayyih W.A, Elhajji F.D, Mima M, Awad R, Arafat T. The influence of eruca sativa (arugula) on pharmaco kinetics of sildenafil in rats. Neuro endocrinology Letters.2017;38:295-300.
- Michael J.G, Jorge R.M.M, José R.G, Carlos M.R, Dharma R.P. Energy drinks and health: A brief review of their effects and consequences. Ciencias de la Conducta.2012;27:23-34.
- Desbrow B, Leveritt M. Well-trained endurance athletes’ knowledge, insight, and experience of caffeine use. International journal of sport nutrition and exercise metabolism.2007;17:328-39.
- Curran C.P, Marczinski C.A. Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain. Birth Defects Research.2017 ; 109:1640-8.
- Chesney R. Taurine: Its biological role and clinical implications. Advances in pediatrics.1985;32:1-42.
- NAKAMuRA T, OGAsAwARA M, KoyAMA I, NEMoTo M, YosHiDA T. The protective effect of taurine on the biomembrane against damage produced by oxygen radicals. Biological and Pharmaceutical Bulletin.1993 ; 16:970-2.
- Mochizuki H, Oda H, Yokogoshi H. Dietary taurine potentiates polychlorinated biphenyl-induced hypercholesterolemia in rats. T he Journal of nutritional biochemistry.2001 ; 12:109-15.
- O’rourke M, Xiong-Jing J. Sildenafil/nitrate interaction. Circulation.2000;101:e90-e.
- McLeod A, McKenna C, Northridge D. Myocardial infarction following the combined recreational use of viagra® and cannabis. Clinical cardiology.2002 ; 25:133-4.
- Bushra R, Aslam N, Khan A.Y. Food-drug interactions. Oman Med J.2011 ; 26:77-83.
- Corbin J.D, Francis S.H, Webb D.J. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urology.2002;60:4-11.
- Jetter A, Kinzig‐Schippers M, Walchner‐Bonjean M, Hering U, Bulitta J, Schreiner P, Sörgel F,Fuhr U. Effects of grapefruit juice on the pharmaco kinetics of sildenafil. Clinical Pharmacology & Therapeutics.2002 ; 71:21-9.
- Stavros F, Kramer W.G, Wilkins M.R. The effects of sitaxentan on sildenafil pharmaco kinetics and pharmacodynamics in healthy subjects. British journal of clinical pharmacology.2010;69:23-6.
- Carrillo J.A, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clinical,pharma cokinetics.2000 ; 39:127-53.
- Shaikhli T.A, Dayyih W.A, Mallah E, Hamad M, Qinna N, Arafat T. Determination of atorvastatin pharmacokinetic parameters by lc/ms-ms with traditional liquorice beverage. Advances in Analytical Chemistry.2015 ; 5:17-24.
- Mallah E, Al Ani N, Dayyih A.W, Awad R. Simultaneous determination of sildenafil and glimepiride in rat plasma by using lc-ms method and their applications in pharmacokinetic interactions. J Clin Pharm.2014 ; 1:1007-20.
- Tbeekh H.T.A, Dayyih W.A.A, Mallah E.M, Qinna N.A, Awad R.M, Arafat T.A. Pomegranate juice affects on pharmacokinetic parameters of metronidazole by using hplc-ms. World J Pharm Pharm Sci.2014 ; 3:150-4.
- Tamimi L, Abudayyih W, Mallah E, Arafat T. Pioglita zone hcllevels and its pharma cokinetic application in presence of sucralose in animals serum by hplc method. Pharm,Anal. Acta,2014;5:2.
- Awad R, Mallah E, Al Khawaja B, Dayyih W.A, El-Hajji F, Matalka K.Z, Arafat T. Pomegranate and licorice juices modulate metformin pharmacokinetics in rats. Neuro endocrinology letters,2016;37.
- Nichols D.J, Muirhead G.J, Harness J.A. Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: Absolute bioavailability, food effects and dose proportionality. British journal of clinical pharmacology.2002 ; 53:5-12.
- BMWP D.A.B, CONSULTATION E, PARTY A.B.B.W. Committee for human medicinal products (chmp).2007.
- Osman M.A, Maghraby E.G.M, Hedaya M.A. Intestinal absorption and presystemic disposition of sildenafil citrate in the rabbit: Evidence for site‐dependent absorptive clearance. Biopharmaceutics & drug disposition.2006 ; 27:93-102.
- Labudova O, Yeghiazarjan C, Höger H, Lubec G. Taurine modulates expression of transporters in rat brain and heart. Amino Acids.1999;17:301-13.
- Lehmann J.M, McKee D.D, Watson M.A, Willson T.M, Moore J.T, Kliewer S.A. The human orphan nuclear receptor pxr is activated by compounds that regulate cyp3a4 gene expression and cause drug interactions. Journal of Clinical Investigation.1998;102:1016.
- Pascussi J.M, Drocourt L, Fabre J.M, Maurel P, Vilarem M.J. Dexamethasone induces pregnane x receptor and retinoid x receptor-α expression in human hepatocytes: Synergistic increase of cyp3a4 induction by pregnane x receptor activators. Molecular Pharmacology.2000;58:361-72.
- Staudinger J.L, Goodwin B, Jones S.A, Hawkins-Brown D, MacKenzie K.I, LaTour A, Liu Y, Klaassen C.D, Brown K.K, Reinhard J. The nuclear receptor pxr is a lithocholic acid sensor that protects against liver toxicity. Proceedings of the National Academy of Sciences.2001;98:3369-74.
- Xie W, Radominska-Pandya A, Shi Y, Simon C.M, Nelson M.C, Ong E.S, Waxman D.J, Evans R.M. An essential role for nuclear receptors sxr/pxr in detoxification of cholestatic bile acids. Proceedings of the National Academy of Sciences.2001 ; 98:3375-80.
- Matsuda H, Kinoshita K, Sumida A, Takahashi K, Fukuen S, Fukuda T, Takahashi K, Yamamoto I, Azuma J. Taurine modulates induction of cytochrome p450 3a4 mrna by rifampicin in the hepg2 cell line. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research.2002 ; 1593:93-8.
- Ueshima Y, Tsutsumi M, Takase S, Matsuda Y, Kawahara H. Acetaminophen metabolism in patients with different cytochrome p‐4502e1 genotypes. Alcoholism: Clinical and Experimental Research.1996; 20.
- Laine J, Auriola S, Pasanen M, Juvonen R. Acetaminophen bioactivation by human cytochrome p450 enzymes and animal micro somes. Xenobiotica.2009 ; 39:11-21.
- Temple J.L, Dewey A.M, Briatico L.N. Effects of acute caffeine administration on adolescents. Experimental and clinical psychopharmacology.2010;18:510.
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Can you crush up Viagra and put it in a drink?
Can you dissolve Viagra in water? – No, Viagra isn’t water-soluble and won’t dissolve well in water. In fact, it’s possible that breaking up the pill and trying to dissolve it might actually make it less effective. However, it is recommended that you take Viagra with water since it can help the pill move through your digestive system easier.
Indigestion or an upset stomach can be a side effect of Viagra and some people have found that taking Viagra with a glass of water reduced the chances of digestive issues. If you have trouble swallowing Viagra, consider investing in a pill splitter that can cleanly divide your pills in half without the risk of shattering the pill or creating excessive dust after the break.
Pill splitters are also much safer than trying to do it yourself with a sharp knife. Viagra was the first ED medication introduced way back in 1996. It’s been very successful, helping millions of people. Viagra is available as oral tablets in three strengths, but a pharmacist can also compound it in other dosage forms, like a chewable or liquid version, though these are not FDA approved.
How can I enhance the effects of Viagra?
Viagra (active ingredient sildenafil ; see Important Safety Information ) is a highly effective, FDA-approved medication used to treat erectile dysfunction (ED), But like any other medication, it’s not a magic pill. If Viagra isn’t achieving the results you desire, you can make changes to make Viagra more effective.
Taking the pill at the right time, not taking it on a full stomach, and avoiding taking it with drug or alcohol use all might improve the effectiveness of the medication. Lifestyle changes and healthy habits may also make Viagra more effective. Whether you’re taking Viagra for the first time or you’re a seasoned pro, continue reading to learn how to make Viagra work best for you.
Viagra treats erectile dysfunction by stopping the chemical reaction that causes blood to leave an erect penis—this is key to understanding how to make Viagra more effective. More specifically, Viagra is a member of a class of drugs called PDE-5 inhibitors,
These work by blocking an enzyme called PDE-5, which encourages blood to flow out of the penis, When PDE-5 is blocked, it keeps the blood vessels in the penis open, allowing blood to flow into the penis more freely, making it easier to get and maintain an erection, PDE-5 inhibitors like Viagra don’t cause an erection automatically.
Sexual arousal is necessary to get an erection on Viagra. So, the first step you can take to boost the effects of Viagra is to set the mood. Several factors can influence how quickly and effectively Viagra works once you take it. Here are some tips that can really help Viagra do its thing.
- If you take Viagra on a full stomach —particularly if you’ve had a heavy, high-fat meal —the medication may take longer to work.
- A full stomach can delay your body’s absorption of Viagra by up to an hour, meaning your erection might come later than expected, be less strong than you want, or not last as long as you’d like.
This doesn’t necessarily mean you need to take Viagra on an empty stomach, but be mindful of taking it too close to full, heavy meals. While it’s safe to drink alcohol with Viagra in moderation, drinking may make it more difficult to get an erection. Alcohol is a depressant that affects many different systems in the body, including those involved in producing an erection.
Alcohol, as well as marijuana and other drugs, can worsen ED symptoms. Chronic heavy drinking damages the liver, heart, and nerves, as well as reduces testosterone —all of which can lead to ED and make it more difficult for Viagra to achieve its desired effect. When it comes to medication, more is not necessarily better.
But, if you’re taking Viagra exactly as you’re supposed to and it still doesn’t work for you, adjusting the dose or switching to a different prescription medication might help. Speak to your healthcare provider so they can make the appropriate adjustments to your prescription (and never take more Viagra than is prescribed to you).
- Ideally, Viagra should be taken 30–60 minutes before you plan to have sex for best results.
- It needs time to work, so taking Viagra too close to the time that you need it may make it more difficult to get an erection strong enough for satisfying sex,
- Taking Viagra too early may do the same.
- Because Viagra works for about four hours before wearing off, taking it too far in advance of sexual activity (say, in the morning when you plan to have sex at night) might not lead to the erection you want.
If you’re new to Viagra, try it out a couple of times solo to see how it affects you. Knowing how you react to Viagra might take some pressure off when it comes to partnered play. Viagra (and erections in general) work best when you’re healthy. A healthy body—particularly a healthy heart—is your best asset in overcoming ED.
- Get enough cardiovascular exercise, A sedentary lifestyle is a major risk factor for erectile dysfunction, especially because it can contribute to heart disease, high blood pressure, and other medical conditions that affect blood flow. One study found that men who were inactive or moderately active (less than 150 minutes of physical activity a week) were as much as 60% more likely to experience ED than men who got at least 150 minutes of physical activity each week.
- Maintain a healthy weight, A large, multi-year study found that obesity nearly doubles a person’s risk for ED. Obesity is also a risk factor for type 2 diabetes, which can damage nerves and blood vessels throughout the body. This includes those that supply the penis, which can result in ED.
- Don’t smoke, Tobacco smoke contains thousands of toxins that can damage the lining of the blood vessels in your body, including the penis. Research has linked cigarette smoking to erectile dysfunction and shown that stopping smoking can help improve symptoms of ED.
If you’re not satisfied with the results of your Viagra, it’s likely you’ve taken to the internet for tips to make the medication work faster (you’re here, after all). While some tips and tricks promise to help you get an erection faster, there is no way to speed up the process of Viagra if you are already taking the medication as prescribed.
Here are some myths about making Viagra work faster. Does chewing make Viagra work faster? The answer is no. These pills are not made to work that way and should be swallowed as a whole, as recommended by the manufacturer of the medication. If you chew your Viagra, the time it takes to fully process the pill either stays the same, or it may even cause the medication to take even longer to help you achieve an erection.
Viagra (and its generic counterpart, sildenafil ) are meant to be swallowed, not dissolved under the tongue. Viagra must pass through the digestive tract in order to work properly. There are sublingual (under the tongue) options on the market that contain sildenafil and other PDE-5 inhibitors.
- While Viagra is extremely effective to help you get or maintain an erection, unfortunately, it doesn’t increase your libido,
- Sexual arousal is needed for the pill to do its job.
- If you struggle with low libido or mismatched libido with a partner, speak to your healthcare provider.
- They may refer you to a sex therapist or explore other medical options to increase your sex drive,
All medications have the potential to cause side effects, and ED medications like Viagra are no different. Common side effects of Viagra tend to be mild and include :
- Dizziness
- Headache
- Flushing
- Upset stomach or indigestion
- Abnormal vision (increased sensitivity to light, blurred vision, or blue-tinted vision)
- Nasal congestion or runny nose
- Back pain
- Insomnia
- Rash
- Muscle pain
Serious side effects of Viagra are less common but require urgent medical attention if experienced. These include:
- Priapism (a prolonged, painful erection that won’t go away)
- Chest pain
- Sudden vision loss
- Ringing in ears or hearing loss
- Seizures
- Swelling in your arms or legs
If you’re taking Viagra but haven’t achieved the desired effects, these tips may make the medication more effective. If all else fails, a different dosage or alternative medication might be a better fit. Speak with your healthcare provider to learn how you can get the most out of your erectile dysfunction medication.
- Arackal, B.S. & Benegal, V. (2007). Prevalence of sexual dysfunction in male subjects with alcohol dependence. Indian Journal of Psychiatry, 49 (2), 109–112. doi:10.4103/0019-5545.33257. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917074/
- Bacon, C.G., Mittleman, M.A., Kawachi, I., et al. (2006). A prospective study of risk factors for erectile dysfunction. The Journal of Urology, 176 (1), 217–221. doi:10.1016/S0022-5347(06)00589-1. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16753404/
- DailyMed. (2017). Viagra- sildenafil citrate tablet, film-coated. Retrieved on Nov.9, 2022 from https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a2a9f459-e692-4e85-83b0-a35fbf35e91b
- Janiszewski, P.M., Janssen, I., & Ross, R. (2009). Abdominal obesity and physical inactivity are associated with erectile dysfunction independent of body mass index. Journal of Sexual Medicine, 6 (7), 1990-1998. doi:10.1111/j.1743-6109.2009.01302.x. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19453892,
- Kovac, J.R., Labbate, C., Ramasamy, R., et al. (2015). Effects of cigarette smoking on erectile dysfunction. Andrologia, 47 (10), 1087–1092. Doi: 10.1111/and.12393. Retrieved from https://pubmed.ncbi.nlm.nih.gov/25557907/
- Smith, B.P. & Babos, M. (2022). Sildenafil. StatPearls, Retrieved on Nov.9, 2022 from https://www.ncbi.nlm.nih.gov/books/NBK558978/
- Zucchi, A., Costantini, E., Scroppo, F.I., et al. (2019). The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue. Andrology, 7 (6), 804–817. doi:10.1111/andr.12683. Retrieved from https://pubmed.ncbi.nlm.nih.gov/31350821/
Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.
How can I absorb Cialis better?
High fat foods – Avoid high fat foods or heavy meals before taking Cialis and before sexual activity. High fat foods can affect how well Cialis works. It may also take longer to work.
Why can’t I stay hard with Cialis?
How Cialis Works: Final Thoughts – Cialis works when you use it correctly most of the time. But when you start messing with the system, those changes and deviations can keep your rocket from achieving liftoff. And that’s just one version of user error that may cause tadalafil to fail you. If you’re taking Cialis, and not getting the results you want, remember some key points:
- Dealing with erectile dysfunction can be a frustrating experience, especially if you don’t get the results you anticipated from medications like Cialis.
- These medications are real, proven, science-backed erectile dysfunction treatments though, and are generally effective when used correctly.
- Using them incorrectly — having the wrong dosage or not following instructions — can cause Cialis not to work.
- Cialis might also fail if your ED is related to psychological issues — performance anxiety, intimacy issues, low self-confidence and depression can all affect your erections.
- FDA-approved prescription medications like Cialis are substantially more safe and effective than supplements and over-the-counter treatments you might get elsewhere.
So if Cialis is failing you, talk to a healthcare provider today about other options. They may adjust your dose, give you some tips or switch you to another medication. Whatever it takes, get your ED under control today, buddy — you deserve to enjoy sex.
- Auerbach, et al. (2012, January). Tadalafil 2.5 or 5 mg administered once daily for 12 weeks in men with both erectile dysfunction and signs and symptoms of benign prostatic hyperplasia: Results of a randomized, placebo-controlled, double-blind study. The journal of sexual medicine. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pubmed/21981682
- Bellastella, et al. (2014, March 6). Diabetes and sexual dysfunction: Current perspectives. Diabetes, metabolic syndrome and obesity : targets and therapy. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949699/
- Buvat, et al. (2015, November 12). Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6-month observational study (EDATE): Impact of patient characteristics and Comorbidities. BMC urology. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643510/
- Center for Drug Evaluation and Research. (n.d.). Questions and answers for Cialis (Tadalafil).U.S. Food and Drug Administration. Retrieved June 10, 2022, from https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/questions-and-answers-cialis-tadalafil
- Costa, et al. (2009, November 3). Tadalafil once daily in the management of erectile dysfunction: Patient and partner perspectives. Patient preference and adherence. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778425/
- : FDA-approved drugs. accessdata.fda.gov. (n.d.). Retrieved June 10, 2022, from https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=021368
- Esfahani, S.B., & Pal, S. (2018, July 12). Obesity, mental health, and sexual dysfunction: A critical review. Health psychology open. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047250/
- Fujimoto, et al. (2007, May). A comparison of the efficacy and tolerability of Tadalafil 10 mg and 20 mg in Japanese patients with severe erectile dysfunction. The journal of sexual medicine. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pubmed/17087800
- Jackson, G. (2013, September). Erectile dysfunction and cardiovascular disease. Arab journal of urology. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442980/
- Labazi, et al. (2012, March). New insights into hypertension-associated erectile dysfunction. Current opinion in nephrology and hypertension. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pubmed/22240443
- Dhaliwal, A, Gupta, M. (2022). PDE5 Inhibitors. In: StatPearls, Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
- Reference ID: 3024692 – food and drug administration. (n.d.). Retrieved June 10, 2022, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021368s20s21lbl.pdf
- Shridharani, A.N., & Brant, W.O. (2016, February). The treatment of erectile dysfunction in patients with neurogenic disease. Translational andrology and urology. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739980/
- Which drug for erectile dysfunction? Harvard Health. (2020, April 10). Retrieved June 10, 2022, from https://www.health.harvard.edu/mens-health/which-drug-for-erectile-dysfunction
- Zinner, N. (2007, January). Do food and dose timing affect the efficacy of sildenafil? A randomized placebo-controlled study. The journal of sexual medicine. Retrieved June 10, 2022, from https://www.ncbi.nlm.nih.gov/pubmed/17233779
What does Cialis not mix with?
Drug Interactions – Cialis can interact with other medications. Talk with your healthcare provider if you’re on any of the following, and always let your prescriber know about all medications and supplements you take:
Alpha blockers : Medications like doxazosin and tamsulosin can interact with Cialis, producing serious side effects such as dangerously low blood pressure. Nitrates : Nitrates, nitroglycerin-based medication, and other medications prescribed to treat chest pain and angina (including amyl nitrite) can cause a serious reaction or even death when combined with Cialis or other similar medications. Riociguat (Adempas) : Guanylate cyclase stimulators like riociguat can cause side effects like dangerously low blood pressure when combined with Cialis. St. John’s wort : Some herbal and over-the-counter remedies can change the level of Cialis in your bloodstream, leading to serious side effects. Make your prescriber aware of any supplements you take. Antibiotics : Some antibiotics, including clarithromycin, erythromycin, and telithromycin, can increase blood levels of Cialis, causing unwanted and sometimes dangerous side effects including low blood pressure or priapism (prolonged erections). Rifampin and other antibiotics may lower the level of Cialis in your blood, reducing its efficacy. Let your prescriber know you are taking Cialis before starting a new antibiotic. HIV medication : Certain HIV medications and protease inhibitors can raise levels of Cialis in your blood, causing unwanted and potentially dangerous side effects, including priapism. Oral antifungals : Some antifungals like ketoconazole and itraconazole may raise Cialis levels in your blood. Other ED medications : Viagra (generic sildenafil ) and Levitra (generic vardenafil) should not be combined with Cialis, as this may increase the risk of side effects.