Levitra: What Are The Alternatives?

Short facts about erectile dysfunction and treatments

  • Erectile dysfunction is a worldwide condition affecting both men and women.
  • Erectile dysfunction is defined as the inability to achieve or maintain an erection of sufficient rigidity for vaginal penetration and completion of the sexual act.
  • The prevalence of erectile dysfunction is anticipated to increase from 152 million in 1995 to 322 million by 2025.
  • Major causes for erectile dysfunction include ageing, cardiovascular diseases such as atherosclerosis and hypertension, diabetes and radical prostatectomy.
  • Before the 1990s most of the erectile dysfunction treatments were surgical therapies.
  • The introduction of oral phosphodiesterase type 5 inhibitors represents the revolution in the non-surgical management of erectile dysfunction.


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History of Levitra

Levitra is a medicine that contains the active substance Vardenafil. It is available as film-coated tablets (5, 10 and 20 mg) and as orodispersible tablets (10 mg). Orodispersible tablets are tablets that dissolve in the mouth.

Levitra contains a phosphodiesterase type 5 inhibitor used in the treatment of erectile dysfunction in men mostly middle-aged. The active ingredient of Levitra, Vardenafil was identified in 1994. Vardenafil was named Levitra by three manufacturers Bayer Pharmaceuticals, GlaxoSmithKline, and Schering-Plough.

The application for the marketing authorization was submitted to the European Agency of Medicines (EMA) in 2001.

In March 2003, Levitra received the marketing authorization from the European Commission and also from regulatory authorities in several Latin America countries. A few months later, in the same year, Levitra was approved by the US Food and Drug Administration (FDA).

Starting with 2005, Bayer received the rights to brand Levitra.


The mechanism of penile erection

The penis physiological states of flaccidity or erection result from the contraction or relaxation, respectively, of smooth muscle cells in the corpus cavernosum.

Penile erection is a spinal reflex that is initiated by autonomic and somatic penile afferents and also by supraspinal influences from visual, olfactory, and imaginary stimuli. There are several central transmitters involved in the erectile control, some of them with a facilitatory role and others with an inhibitory role.

The central transmitters with a facilitatory role in the penile erection are:

  • Dopamine
  • Acetylcholine
  • Nitric Oxide (NO)
  • Peptides, such as Oxytocin and Adrenocorticotropin/α-melanocyte-stimulating hormone.

The central transmitters that inhibit the penile erection are serotonin which may be either facilitatory or inhibitory, and enkephalins which are inhibitory.

The degree of contraction of the smooth muscle cells in the corpus cavernosa is determinate by the balance between contracting and relaxant factors. Noradrenaline contracts both smooth muscle of the corpus cavernosum and penile vessels via stimulation of α1-adrenoceptors, while nitric oxide is considered the most important factor for relaxation of penile vessels and corpus cavernosum.

Nitric oxide is released during sexual stimulation. It activates the enzyme called guanylate cyclase, resulting in an increased level of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum. This, in turn, results in smooth muscle relaxation, allowing increased inflow of blood into the penis. The level of cyclic guanosine monophosphate is regulated by the rate of synthesis via guanylate cyclase and by the rate of degradation via cyclic guanosine monophosphate hydrolysing phosphodiesterases (PDEs).


How does Levitra work in the treatment of erectile dysfunction?

Like other phosphodiesterase type 5 inhibitors, Levitra is not effective in the absence of sexual stimulation. Levitra acts by increasing the blood flow in the penis and improves the erectile function in men with erectile dysfunction.

Vardenafil is a potent and selective inhibitor of the cyclic guanosine monophosphate-specific phosphodiesterase type 5 (PDE5), the most prominent phosphodiesterase in the human corpus cavernosum responsible for degradation of cyclic guanosine monophosphate. During sexual stimulation, the release of nitric oxide from nerve terminals and endothelial cells determinates the relaxation of the penile arteries and corpus cavernosa smooth muscle by increasing the penile blood flow. The release of nitric oxide stimulates the synthesis of cyclic guanosine monophosphate in the smooth muscle cells. The increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection.





Levitra is a fast acting medicine to treat erectile dysfunction.

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About Levitra

At least one in ten men has trouble getting an erection at some time. Levitra helps men to get and maintain an erection when sexually stimulated and/or excited. The medicine relaxes the blood vessels in the penis which results in more blood flowing to the penis. It reduces the action of the natural chemical in your body that makes erections go away.

How to take it?

You should take Levitra 25 minutes to 1 hour before intercourse. Within a window of 25 minutes to 4-5 hours after you take the medicine, it will be easier to keep and maintain an erection when you are sexually excited. If you take this medicine with food it may slow its action down and reduce its effectiveness.

This medicine will only work when you’re sexually excited. You won’t get an erection just by taking Levitra.

What dose should I take?

The best starting dose for Levitra is 10 mg tablets, however this dose can be adjusted according to the response. The maximum dose is 20mg and a lower dose of 5mg may also be taken by those who experience side effects.

Patient Information Leaflet

Always read the patient information leaflet before commencing treatment. The Patient Information leaflets can be found here for 5mg, 10mg and 20mg dosages.


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Pharmacokinetic properties of Levitra

According to the bioequivalence studies, the pharmacokinetic profile of Levitra film-coated tablets is different from the pharmacokinetic profile of Levitra orodispersible tablets.


  • Absorption

In Levitra film-coated tablets, the active ingredient Vardenafil is rapidly absorbed. The maximum observed plasma concentrations were reached in some men as early as 15 minutes after oral administration. However, 90% of the time, maximum plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state.

The rate of absorption of vardenafil film-coated tablets is reduced by high-fat meals (containing 57% fat).

After oral administration of Levitra orodispersible tablets without water, vardenafil is rapidly absorbed. The median time to reach the maximum plasma concentration varied between 45 to 90 minutes and was similar or slightly delayed (by 8 to 45 min) compared to the film-coated tablets.


  • Distribution

The mean volume of distribution for Vardenafil is 208 l, indicating distribution into tissues. Vardenafil and its major circulating metabolite (M1) are highly bound to plasma proteins (approximately 95% for vardenafil or M1).


  • Biotransformation

Levitra film-coated tablets are metabolised predominantly by hepatic metabolism via cytochrome P450 (CYP) isoform 3A4 with some contribution from CYP3A5 and CYP2C isoforms.

In humans, the one major circulating metabolite (M1) results from desethylation of vardenafil and is subject to further metabolism with a plasma elimination half-life of approximately 4 hours. Parts of M1 are in the form of the glucuronide in the systemic circulation. Metabolite M1 shows a phosphodiesterase selectivity profile similar to vardenafil and an in vitro potency for phosphodiesterase type 5 of approximately 28% compared to vardenafil, resulting in an efficacy contribution of about 7%.


  • Elimination

The total body clearance of vardenafil is 56 l/h with a resultant terminal half-life of approximately 4-5 hours. After oral administration, vardenafil is excreted as metabolites predominantly in the faeces (approximately 91-95% of the administered dose) and to a lesser extent in the urine (approximately 2-6% of the administered dose).




What are the side effects of Levitra?

Like all other drugs, Levitra can cause side effects, although not everybody gets them. Most of the effects are mild or moderate.


Very common side effects (may affect more 1 in 10 patients) include:

  • Headaches.


Common side effects (may affect up to 1 in 10 patients) include:

  • Dizziness,
  • Flushing,
  • Blocked or a runny nose,
  • Indigestion.


Uncommon side effects (may affect up to 1 in 100 patients) include:

  • Effects on vision; redness of the eye, effects on colour vision, eye pain and discomfort, light sensitivity,
  • Ringing in the ears; vertigo,
  • Fast heartbeat or pounding heart,
  • Breathlessness,
  • Stuffy nose,
  • Acid reflux, gastritis, abdominal pain, diarrhoea, vomiting; feeling sick (nausea), dry mouth,
  • Raised levels of liver enzymes in your blood,
  • Rash, reddened skin,
  • Back or muscle pain; increase in the blood of a muscle enzyme (creatine phosphokinase), muscle stiffness,
  • Prolonged erections,
  • Malaise.


Rare side effects (may affect up to 1 in 1000 patients) include:

  • Inflammation of the eyes (conjunctivitis),
  • Allergic reaction,
  • Anxiety,
  • Fainting,
  • Amnesia,
  • Seizure,
  • Increase pressure in the eye (glaucoma),
  • Effects on the heart (such as heart attack, altered heartbeat or angina),
  • High or low blood pressure,
  • Nosebleed,
  • Effect on results of blood tests to check liver function,
  • Sensitivity of the skin to sunlight,
  • Painful erections,
  • Chest pain.


Very rare or unknown side effects (may affect less than 1 in 10000 patients) include:

  • Haematuria (blood in the urine),
  • Penile Haemorrhage (penile bleeding),
  • Haematospermia (presence of blood in the semen).


Stop taking Levitra and contact your doctor immediately if you experience a partial, sudden, temporary or permanent decrease or loss of vision in one or both eyes.


Facts that you should take into consideration before taking Levitra

Before taking Levitra, tell you should tell your doctor or your pharmacist if you suffer or ever suffered from:


  • heart problems such as angina, heart failure, irregular heartbeats, or have had a heart attack,
  • low blood pressure or have high blood pressure that is not controlled,
  • pulmonary hypertension,Portrait of thinking man
  • stroke,
  • seizure,
  • liver problems,
  • kidney problems and require dialysis,
  • retinitis pigmentosa, a rare genetic (runs in families) eye disease,
  • severe vision loss, or if you have an eye condition called non-arteritic anterior ischemic optic neuropathy (NAION),
  • stomach ulcers,
  • bleeding problem,
  • deformed penis shape or Peyronie’s disease,
  • erection that lasted more than 4 hours,
  • blood cell problems such as sickle cell anaemia, multiple myeloma, or leukaemia,
  • hearing problems.


Alternatives to Levitra

Other medications

Levitra is just one of a number of medications used in the treatment of erectile dysfunction – Most of them can be bought here at Assured Pharmacy (if you need any peace of mind using an online pharmacy). These include Viagra (Sildenafil), Levitra (Vardenafil)Cialis (Tadalafil). Viagra Connect has also recently been released in the U.K. All of which have similar, but noticeably different effects and side-effects which are noted and discussed here.

Lifestyle changes

The following changes may be helpful for patients with erectile dysfunction:

  • eating a balanced diet;
  • maintaining a healthy body weight;
  • engaging in regular exercises;
  • quitting smoking;
  • avoiding too much alcohol and illicit drugs;
  • seeking help for emotional and physiological issues.


Natural remedies for erectile dysfunction

Be weary of what natural remedies you come across online, Kamagra, for example, is marketed as a cure for erectile dysfunction but is illegal and unregulated in the U.K.

  • Arginine

L-arginine is an amino acid which occurs naturally in food, boosts the body’s production of nitric oxide, a compound that facilitates erections by dilating blood vessels in the penis.

Several studies have shown the effectiveness of L-arginine against erectile dysfunction. A trial published in 1999 found that high doses of L-arginine can help improve sexual function, but only in men with abnormal nitric oxide metabolism, such as that associated with cardiovascular disease.

In another study, published in 2003 the researchers showed that patients diagnosed with erectile dysfunction who took L-arginine along with the pine extract pycnogenol saw major improvements in sexual function with no side effects.

  • Ginseng

Ginseng is the most common ingredient among top-selling supplements for men’s sexual health.

Red ginseng has been reported to improve erectile function in a rat model of metabolic syndrome and it was also found to inhibit fibrosis of the corpus cavernosum of the penis.

  • Yohimbine

Yohimbine is an indole alkaloid derived from the bark of the African Yohimbe tree. The mechanism of action consists of inhibition of inhibition of central alpha-2-adrenergic receptors, decreasing central inhibition of arousal, and increasing penile nerve stimulation resulting in increased level of nitric oxide. Seven placebo-controlled studies have been shown that yohimbine is superior to placebo for the treatment of erectile dysfunction with rare adverse events.

  • Horny goat weed goat

The horny goat weed is a flowering perennial plant found throughout Asia and parts of the Mediterranean. Its active ingredient is called icariin, a flavonol glycoside which is known to improve cardiovascular function, hormone regulation, modulation of immunological function and antitumor activity. Icariin has also been shown to have a phosphodiesterase type 5 inhibitor effects. Animal studies have been carried out showing improvements in penile hemodynamic parameters.

  • Ginkgo Biloba

Ginkgo Biloba is known to improve memory enhancement in geriatric population and also to improve claudication distance and cutaneous ulcers in patients with the peripheral vascular disease.

Ginkgo Biloba extract is proposed to induce nitric oxide in endothelial cells and thus causing relaxation of vascular smooth muscles. Relaxation of rabbit corpus cavernosal smooth muscle cells with the use of Ginkgo Biloba have been reported in animal studies.

The adverse effects of Ginkgo Biloba include headaches, major bleeding (in a patient who is taking warfarin concurrently) and seizures with reported fatalities.



New therapy alternatives for erectile dysfunction

  • Soluble guanylate cyclase activators

In some patients, the low endogenous nitric oxide formation and the increased oxidative stress can inactivate the nitric oxide and inhibit the activity of guanylate cyclase. For this reason, in these patients, the effectiveness of phosphodiesterase type 5 inhibitors is significantly reduced.

A new class of agents called soluble guanylate cyclase activators have been shown to increase the activity of guanylate cyclase.

A study using an in vivo model using human corpus cavernosa tissue from 16 patients who did not respond to phosphodiesterase type 5 inhibitors found that combination of soluble guanylate cyclase stimulator and vardenafil enhanced relaxation of the corpus cavernosa.

  • Stem cells

Three types of stem cells are commonly used in erectile dysfunction treatment: adipose tissue-derived stem cells, bone marrow-derived stem cells, and muscle-derived stem cells.

Therapy with stem cells represents an alternative for reducing the transitory effect of phosphodiesterase type 5 inhibitors. Stem cell regenerative therapy is based on the rationale that stem cells can differentiate into a wide variety of cells including endothelial cells, Schwann cells, smooth muscle cells, and neurons.

The efficacy of stem cells in erectile dysfunction treatment has been studied in several animal models and also in human subjects. One study included 7 diabetic men aged between 57 and 87 who were treated with an intracavernosal injection of 15 million allogeneic umbilical cord blood stem cells. Morning erection was regained in six out of the seven men at 6 months from time of injection. No adverse events were reported.

In another study, bone marrow-mononuclear cells have been shown to be effective in erectile dysfunction treatment. The study included 12 patients who received escalating doses of bone marrow mononuclear cells. After 6 months, there were reported significant improvements of intercourse satisfaction and erectile function.

  • Close-up on discussion. Close-up of people communicating while sGene therapy 

Gene-based therapy has been proposed as a potential new therapy for patients with erectile dysfunction who do not respond to phosphodiesterase type 5 inhibitors. Since the nitric oxide principally contributes to the relaxation of the cavernous smooth muscle, genes involved in nitric oxide synthesis such as nitric oxide synthase (NOS), protein inhibitor of NOS (PIN), anti-arginase, cGMP-dependent protein kinase G1 have been tested for potential gene therapies of erectile dysfunction. Gene therapy has the role to enhance production or nitric oxide-mediated signalling pathways, growth factor-mediated nerve regeneration or K+ channel activity in the smooth muscle.

An important advantage of gene therapy is the fact that the genetic material can be easily injected into the penis, avoiding potential systemic complications. Furthermore, the effects of gene therapy are more prolonged in the penis because of a slow turnover rate of the tunica albuginea (tough fibrous layer of connective tissue that surrounds the corpus cavernosa of the penis).

  • Low-intensity shockwave therapy 

Low-intensity extracorporeal shockwave therapy (Li-ESWT) represents a novel and promising treatment modality for erectile dysfunction. It is a non-invasive therapy and uses acoustic waves, which can pass through tissue and be focussed to target specific areas or organs to induce the desired effects. The mechanism of action for this therapy consists of sending acoustic waves that generate pressure impulses, which can treat patients with kidney stones, tendinitis, and peripheral vascular disease.  The mechanisms by which this therapy enhances erectile function are unclear, but hypotheses include stimulation of neoangiogenesis, recruitment of stem cells and Schwann cell activation leading to nerve regeneration.

LiESWT has been suggested to improve the effect of phosphodiesterase type 5 inhibitors in men who have previously not responded to this treatment.

The major advantage of LiESWT therapy is the possibility to restore natural erections.



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