Trade name of the drug: Cyclone DX

Active ingredients (INN): sildenafil citrate and dapoxetine hydrochloride

Dosage Form: Coated Tablet

Composition:

One tablet contains

Active ingredient: sildenafil 50/100 mg, dapoxetine 30/60 mg.

Excipients: corn starch, lactose, povidone (PVP-K-30), isopropyl alcohol, purified talc, magnesium stearate, croscarmellose sodium, colloidal anhydrous silicon, water indigo carmine dye, purified water.

Description : Blue diamond-shaped film-coated tablets, smooth on both sides.

Pharmacotherapeutic group: Drugs for the treatment of erectile dysfunction. Preparations prolonging sexual intercourse.

ATX code: G04BE

 

Pharmacological properties

Sildenafilis a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP in the corpora cavernosa. Sildenafil does not have a direct relaxing effect on the corpora cavernosa, but actively enhances the relaxing effect of nitric oxide on this tissue. With sexual arousal, the local release of NO under the influence of sildenafil leads to inhibition of PDE5 and an increase in the level of cGMP in the corpus cavernosum, resulting in relaxation of smooth muscles and increased blood flow in the corpus cavernosum.

Sildenafil can cause mild and transient color discrimination (blue / green). The supposed mechanism of color vision impairment is the inhibition of PDE6, which is involved in the process of light transmission in the retina. In vitro studies have shown that the effect of sildenafil on PDE6 is 10 times lower than its activity against PDE5.

In vitro studies indicate that the activity of sildenafil against PDE5 is 10-10000 times higher than its activity against other phosphodiesterase isoforms (PDE 1, 2, 3, 4 and 6). In particular, the activity of sildenafil against PDE5 is 4000 times higher than its activity against PDE3, a cAMP-specific phosphodiesterase involved in cardiac contraction.

Dapoxetine blocks the reuptake of serotonin, which has been clinically proven to effectively combat the problem of premature ejaculation  (PE) in men over the age of 18. Approximately 27-34 percent of all men in different age groups have problems with PE. Most men ejaculate sooner than they realize.

It is clinically proven that the drug Dapoxetine can prolong sexual intercourse by 200-400 percent. SSRIs (Selective Serotonin Reuptake Inhibitors-SSRIs) act by blocking receptors in the brain that absorb the chemical serotonin. Studies have shown that the neurotransmitter serotonin affects mood. SSRIs, by blocking the reabsorption of serotonin, can improve mood, behavior and outlook. But for many people, this is also a cause for concern. SSRIs are selective and only affect serotonin, without affecting other neurotransmitters.

 

Pharmacokinetics

Sildenafil is rapidly absorbed after oral administration. Absolute bioavailability averages 40% (25-63%). After a single oral dose of 100 mg, Cmax is 18 ng / ml and is achieved when taken on an empty stomach for 30-120 minutes. When taking sildenafil in combination with fatty foods, the rate of absorption is reduced; Тmax increases by 60 minutes, and Cmax decreases by an average of 29%. The Vd of sildenafil in an equilibrium state averages 105 liters. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (average 188 ng) was found in semen 90 minutes after taking sildenafil.

Sildenafil is metabolized mainly by the action of microsomal liver isoenzymes CYP3A4 (main pathway) and CYP2C9.

The main circulating metabolite, which is formed as a result of the N-desmethylation of sildenafil, undergoes further metabolism. In terms of the selectivity of action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil itself. The plasma concentration of the metabolite is approximately 40% of that of sildenafil. N-desmethylmetabolite undergoes further metabolism; its terminal T1 / 2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l / h, and T1 / 2 in the terminal phase is 3-5 hours.After oral administration, sildenafil is excreted as metabolites mainly with feces (approximately 80% of the dose) and, to a lesser extent, with urine ( approximately 13% of the dose).

In elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of the free active substance in the plasma is approximately 40% higher than its concentration in young (18-45 years) patients.

In renal failure mild (CC 50-80 ml / min) and moderate (CC 30-49 ml / min) severity, the pharmacokinetic parameters of sildenafil after oral administration of a single dose (50 mg) do not change. In severe renal failure (CC ≤ 30 ml / min), the clearance of sildenafil decreases, which leads to an approximately twofold increase in AUC (100%) and Cmax (88%) compared with those in patients with normal renal function in patients of the same age group.

In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group …

Dapoxetine hydrochloride has a characteristic pharmacokinetic profile. Other SSRIs are most effective in at least two weeks, while Dapoxetine hydrochloride reaches its maximum plasma concentration in less than an hour after ingestion and is completely eliminated from the body within one to two hours.

In the next 24 hours (after taking the drug), its concentration in blood plasma is less than 5 percent of the maximum. The drug is quickly absorbed and excreted from the body, which allows you to take it daily.

Dapoxetine is metabolized within 2-3 hours, its plasma level decreases by about 50 percent of the maximum concentration. Thus, the optimal effect is achieved after 30 minutes after taking the drug.

Indications for use

Cyclone DX is indicated for adult men with erectile dysfunction along with premature ejaculation, who are unable to achieve or maintain an erection of the penis and are unable to control ejaculation sufficient for successful intercourse.

Cyclone DX is indicated for adult men with erectile dysfunction who are unable to achieve or maintain an erection of the penis sufficient for successful intercourse.

Cyclone DX is indicated for adult men with premature ejaculation who are unable to control ejaculation sufficient for successful intercourse.

 

Method of administration and dosage

Cyclone DX is used internally.

You must first consult your doctor before taking this medication. It is taken orally about 1 hour before planned sexual activity. A single dose is 50 mg sildenafil / 30 mg dapoxetine. Taking into account the effectiveness and tolerability, the dose can be increased to 100 mg sildenafil / 60 mg dapoxetine 100 mg. The maximum single dose is 100 mg sildenafil / 60 mg dapoxetine 100 mg. The maximum frequency of use is 1 time / day.

Side effects

Sildenafil:

From the side of the central nervous system : headache, hot flashes, dizziness, insomnia are possible.

From the digestive system : possible dyspepsia, asthenia, diarrhea, abdominal pain, nausea.

From the musculoskeletal system : arthralgia, myalgia, increased muscle tone.

Respiratory system : nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, respiratory failure.

From the side of the organ of vision : changes in vision (mild and transient; mainly a change in the color of objects, as well as increased perception of light and impaired clarity of vision), conjunctivitis.

Others : possible flu-like syndrome, the development of infectious diseases, symptoms of vasodilation, back pain, rash, urinary tract infections, dysfunction of the prostate gland; in isolated cases – priapism.

Dapoxetine :

Nausea in 8.7 percent of men who received a low dose (60mg) and 20 percent of men who received a large dose of Dapoxetine

Headache in 5.9 percent of men who received a low dose and 6.8 percent of men who received a large dose of Dapoxetine

Diarrhea in 6.8 percent of men who received a high dose of Dapoxetine

Dizziness in 6.2 percent of men who received a high dose of Dapoxetine

If you feel dizzy or nauseous, see your doctor.

Consult your doctor about any side effects of the drug.

 

Contraindications

Sildenafil citrate

• Hypersensitivity to the active substance or any of the excipients.
• In accordance with its known effect on the nitric oxide / cyclic guanosine monophosphate (cGMP) pathway, sildenafil enhances the hypotensive effect of nitrates, therefore, its combined use with nitric oxide donors (for example, amyl nitrite) or nitrates in any form is contraindicated.
• Erectile dysfunction medications, including sildenafil, should not be used in people for whom sexual activity is inappropriate (for example, people with severe cardiovascular disease such as unstable angina pectoris or severe heart failure).
• It is contraindicated in patients who have vision loss in one eye due to anterior non-arteritis ischemic neuropathy of the optic nerve (NAION), regardless of whether the episode was associated with previous exposure to a PDE5 inhibitor.
• The safety of sildenafil has not been studied in the following patient subgroups and its use is therefore contraindicated: severe hepatic impairment, arterial hypotension (blood pressure <90/50 mm Hg), recent history of stroke or myocardial infarction, and known hereditary retinal degenerative disorders such as retinal pigmentosa retinitis (a minority of these patients have a genetic disorder of the retinal phosphodiesterase).

 

Dapoxetine hydrochloride

• Hypersensitivity to the active substance or any of the excipients.
• Significant pathological heart diseases such as:
• Heart failure (NYHA class II-IV);
• Abnormalities of the conduction system, such as AV block or sick sinus syndrome;
• Significant ischemic heart disease;
• Significant valvular disease;
• History of fainting.
• A history of mania or severe depression.
• Simultaneous treatment with monoamine oxidase inhibitors (MAO), or within 14 days after stopping the drug with MAOIs. Likewise, treatment with MAOIs should not be continued for 7 days after dapoxetine has been discontinued.
• Concomitant therapy with thioridazine, or within 14 days of stopping treatment with thioridazine. Likewise, thioridazine treatment should not be continued for 7 days after dapoxetine has been discontinued.
• Concomitant treatment with serotonin reuptake inhibitors [selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs)] or other medicinal / herbal products with serotonergic effects [eg, L-tryptophan, tramadol, linezolid, lithium, St. John’s wort)] or within 14 days after stopping the drug with these medicinal / herbal products. Likewise, these medicinal / herbal products should not be taken within 7 days of stopping dapoxetine.
• Concomitant treatment with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazadone, nelfinavir, atazanavir, etc.
• Moderate to severe liver failure.

 

Drug interactions

Since Cyclone DX contains sildenafil and dapoxetine, it can enter into interactions characteristic of each of its components.

Sildenafil.

With the simultaneous use of CYP3A4 inhibitors ( erythromycin , cimetidine), the clearance of sildenafil decreases, the concentration of sildenafil in the blood plasma increases.

With the simultaneous use of indinavir, saquinavir, ritonavir, the Cmax in the blood plasma and the AUC of sildenafil increase, which is due to the inhibition of the CYP3A4 isoenzyme under the influence of  indinavir , saquinavir, ritonavir.

Stronger inhibitors of the CYP3A4 isoenzyme such as ketoconazole or itraconazole can be expected to increase plasma concentrations of sildenafil

When used simultaneously with nitrates, the hypotensive effect of nitrates is enhanced.

A case of the development of symptoms of rhabdomyolysis after a single dose of sildenafil in a patient receiving simvastatin is described .

Dapoxetine should not be taken with drugs:
– Monoamine oxidase inhibitors (MAOIs)
– Thioridazine (for the treatment of schizophrenia)
– Lithium (used to treat bipolar disorder (Kerry
Katona)) – Linezolid – an antibiotic
– Tryptophan – a sleeping pill
– St. John’s Wort – herbal medicine
– Tramadol – a strong painkiller
– Medicines used to treat migraine
– Nefazodone – antidepressant

Do not take Dapoxetine at the same time as any of these drugs. In addition, you must stop taking any of the above drugs at least 14 days before you start taking Dapoxetine. After discontinuation of Dapoxetine, the resumption of any of the above drugs is possible in at least 7 days.

It is also not recommended to combine Dapoxetine with:
– Certain drugs used to treat fungal infections, including ketoconazole and itraconazole.
– Certain drugs used to treat HIV infection, including ritonavir, saquinavir, nelfinavir, and atazanavir.
– Certain drugs used to treat infections, including telithromycin.

Do not take Dapoxetine if you are taking any of the drugs listed above.

Consult your doctor for the compatibility of Dapoxetine with other medicinal products.

 

special instructions

Sildenafil.

Before you start taking sildenafil, you should have a cardiovascular examination.

It should be used with caution in patients with anatomical deformity of the penis (for example, angulation, cavernous fibrosis or Peyronie’s disease) and people with diseases that predispose to the development of priapism (such as sickle cell anemia, multiple myeloma or leukemia).

Should not be used in patients for whom sexual activity is undesirable.

Use with caution in patients with a tendency to bleeding, with gastric ulcer and duodenal ulcer in the acute phase, with hereditary retinitis pigmentosa.

In experimental studies, no evidence of the carcinogenicity of sildenafil was found. Bacterial and in vivo mutagenicity tests were negative.

Sildenafil is not used in patients under the age of 18 years.

Dapoxetine.

The drug does not protect against unwanted pregnancy or the transmission of sexually transmitted diseases such as HIV (human immunodeficiency virus).

Sexual activity increases the burden on the heart, which can be dangerous in the presence of cardiovascular disease.

If you experience chest pain during sexual activity, see your doctor.

In case of sudden deterioration or loss of vision, seek emergency medical attention from your doctor. Drinking alcohol can increase the potential side effects of the drug.

 

Overdose

Symptoms – side effects may increase.

Treatment is symptomatic. There is no specific antidote.

 

Release form:

Aluminum / PVC blister, 1×1 or 1×4 in carton with instructions.

 

Storage conditions

Store in a dark place at a temperature not exceeding 25 ° C.

 

Shelf life

2 years.

 

Conditions of dispensing from pharmacies

On prescription.