CEKLON DX

INSTRUCTIONS FOR USE 

CYCLONE DX

CEKLON DX 

 

Trade name of the drug :  Cyclone DX

Active ingredients (INN):  sildenafil citrate and dapoxetine hydrochloride

Dosage form:   film-coated tablet

Composition:

One tablet contains

Active substance:  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, indigo carmine aqueous dye, purified water.

Description :  Diamond-shaped, blue, film-coated tablets, smooth on both sides.

Pharmacotherapeutic group:  Drugs for the treatment of erectile dysfunction. Drugs that prolong sexual intercourse.

Code ATH: G04BE

 

Pharmacological properties

Sildenafil  is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP in the corpus cavernosum. Sildenafil does not have a direct relaxing effect on the corpus cavernosum, but actively enhances the relaxing effect of nitric oxide on this tissue. During sexual arousal, 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 may cause mild and transient impairment of color discrimination (blue/green). The putative mechanism for 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 on PDE5.

In vitro studies indicate that the activity of sildenafil against PDE5 is 10-10,000 times greater 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 greater than its activity against PDE3, a cAMP-specific phosphodiesterase involved in heart contraction.

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

It has been clinically proven that the drug Dapoxetine can prolong sexual intercourse by 200-400 percent. SSRIs (Selective Serotonin Reuptake Inhibitors-SSRIs) work by blocking receptors in the brain that absorb the chemical serotonin. Research has shown that the neurotransmitter serotonin affects mood. SSRIs, by blocking the process of serotonin re-absorption, can improve mood, behavior and outlook. But for many people it also becomes a cause of concern. SSRIs are selective and affect only 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; Tmax increases by 60 minutes, and Cmax decreases by an average of 29%. The Vd of sildenafil at steady state is on average 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 (mean 188 ng) was detected in semen 90 minutes after sildenafil administration.

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

The main circulating metabolite, which is formed as a result of N-desmethylation of sildenafil, undergoes further metabolism. In terms of 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 concentration of the metabolite in plasma is approximately 40% of that of sildenafil. The N-desmethyl metabolite 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 in the form of metabolites mainly in feces (approximately 80% of the dose) and to a lesser extent in 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 plasma is approximately 40% higher than its concentration in young (18-45 years) patients.

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

In patients with liver cirrhosis (Child-Pugh class A and B), the clearance of sildenafil is reduced, resulting in 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 reach their greatest effectiveness after at least two weeks, while Dapoxetine hydrochloride reaches its maximum plasma concentration in less than an hour after administration and is completely eliminated from the body within one to two hours.

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

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

 

Indications for use

Cyclone DX is indicated for adult men with erectile dysfunction who are unable to achieve or maintain a penile erection sufficient for successful sexual intercourse.

 

Directions for use and doses

Cyclone DX is used orally.

You should consult your doctor first before taking this drug. Take orally approximately 1 hour before planned sexual activity. A single dose is 50 mg of sildenafil. Taking into account effectiveness and tolerability, the dose can be increased to 100 mg or reduced to 25 mg. The maximum single dose is 100 mg. The maximum frequency of use is 1 time/day.

For elderly patients over the age of 65 years and with concomitant renal or hepatic impairment, the dose is 25 mg.

 

Side effects

Sildenafil:

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

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

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

From the respiratory system : nasal congestion, pharyngitis, rhinitis, sinusitis, respiratory tract infections, breathing problems.

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

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

Dapoxetine :

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

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

Diarrhea in 6.8 percent of men who received high dose Dapoxetine

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

If you experience dizziness or nausea, consult your doctor.

Consult your doctor about side effects of the drug.

 

Contraindications

Sildenafil Citrate

• Hypersensitivity to the active substance or any of the excipients.
• Consistent with its known effects on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, sildenafil potentiates the hypotensive effects of nitrates and therefore its concomitant use with nitric oxide donors (eg, 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, patients with severe cardiovascular disease such as unstable angina or severe heart failure).
• It is contraindicated in patients who have vision loss in one eye due to nonarteritic anterior ischemic optic neuropathy (NAION), whether or not the episode was related to 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, hypotension (blood pressure <90/50 mmHg), recent history of stroke or myocardial infarction, and known hereditary retinal degenerative disorders such as retinitis (a minority of these patients have genetic disorders of retinal phosphodiesterases).

 

Dapoxetine hydrochloride

• Hypersensitivity to the active substance or any of the excipients.
• Significant pathological heart disease such as:
• Heart failure (NYHA class II-IV);
• Conduction system abnormalities such as AV block or sick sinus syndrome;
• Significant coronary heart disease;
• Significant valve defect;
• History of fainting.
• A history of mania or severe depression.
• Concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days after stopping the drug with MAOIs. Likewise, treatment with MAOIs should not be administered within 7 days after dapoxetine has been discontinued.
• Concomitant therapy with thioridazine, or within 14 days of stopping treatment with thioridazine. Likewise, treatment with thioridazine should not be administered within 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, triptans, tramadol, linezolid, lithium, St. John’s wort)] or within 14 days of 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 strong CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazadone, nelfinavir, atazanavir, etc.
• Moderate and severe liver failure.

 

Drug interactions

Because Cyclone DX contains sildenafil and dapoxetine, it may have interactions specific to each of its components.

Sildenafil.

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

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

Stronger CYP3A4 inhibitors, 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 has been described.

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

Dapoxetine should not be taken simultaneously with any of these drugs. In addition, it is necessary to stop taking any of the above medications at least 14 days before starting to take Dapoxetine. After stopping taking Dapoxetine, resuming any of the above drugs is possible after 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 medications listed above.

For questions regarding the compatibility of Dapoxetine with other medications, consult your doctor.

 

special instructions

Sildenafil.

Before starting to take sildenafil, you should conduct an examination of the cardiovascular system.

Use with caution in patients with anatomical deformation of the penis (such as 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 peptic ulcer of the stomach and duodenum in the acute phase, with hereditary retinitis pigmentosa.

Experimental studies have found no evidence of carcinogenicity of sildenafil. Bacterial and in vivo mutagenicity tests were negative.

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

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 stress on the heart, which can be dangerous if you have cardiovascular disease.

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

If there is sudden deterioration or loss of vision, seek emergency medical attention from your doctor. Drinking alcohol may increase the possible side effects of the drug.

 

Overdose

Symptoms – possible  increased side effects.

Treatment is symptomatic. There is no specific antidote.

 

Release form:

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

 

Food conditions

Store in a dark place at a temperature not exceeding 25°C. Keep away from children.

 

 

Best before date

2 years.

 

Conditions for dispensing from pharmacies

On prescription.

 

Manufacturer

Avison Pharmaceutical Pvt. Ltd., India

Coral Laboratories Limited

Plot № . 27-28, Pharmacity, Selaqui,

Dehradun, Uttarakhand – 248197, India