masteron hair loss

Posted on 08/24/2016  in Articles

The action of isosorbide dinitrate can be due to relaxation of vascular smooth muscle cells in the veins, arteries and arterioles. Postcapillary vessels and major arteries relax to a greater extent than the small arterioles. Dilation of postcapillary vascular bed leads to venous blood depositary that, in turn, decreases venous return to the heart. As a result, filling pressure and left masteron hair loss ventricular wall stress decreased (decrease in preload) and decreases myocardial energy and oxygen.Decreased cardiac filling pressure and reduced wall stress contribute to an increase in capillary blood flow and opening previously sealed intramural coronary vessels, as well as improving the supply of oxygen ischemic subendocardial area. Dilation precapillary vessels leads to a decrease in systolic aortic pressure and peripheral vascular resistance (load reduction). Consequently, the reduced left ventricular cardiac output and myocardial oxygen demand. In heart failure, myocardial oxygen demand to additionally increase due to an increase in cardiac output. Direct koranarnyh dilation of blood vessels and eccentric coronary stenosis, as well as a slight decrease in coronary vascular resistance causes improved myocardial perfusion, leading to improved myocardial oxygen supply. A “symptom steal” independent even from a slight decrease in coronary vascular resistance, not shown.

CONTRAINDICATIONS:

Izoket retard should not be administered in cases of:

  • acute myocardial infarction;
  • in all cases, reduce cardiac filling pressure, acute circulatory failure (shock, circulatory collapse);
  • severe hypotension (systolic blood pressure below 90 mm Hg. Art.).

SIDE EFFECTS:

Early treatment with masteron hair loss nitrates may appear headache, but experience shows that usually after a few days, with incessant taking the drug, it passes. Lowering blood pressure, sleepiness, and increased heart rate may occur during the first days of treatment. Other possible side effects may be nausea, vomiting, erythema (redness). If during treatment the patient takes alcohol can worsen the side effects and reduced therapeutic effect of the drug.

Interactions with other drugs:

The antihypertensive effect Izoket retard may potentiate the simultaneous use of other vasodilators, antihypertensive agents, calcium antagonists, cyclic antidepressants, monoamine oxidase inhibitors and alcohol. When concomitant administration of isosorbide dinitrate and dihydroergotamine, the last level in the blood can increase, leading to a strengthening of its hypotensive action.

DOSAGE AND ADMINISTRATION:

When administered orally, the dosage depends largely on the stage of the disease and the individual requirements in nitrates. With long-term treatment and the absence of other regulations recommend the following dosage:

  • Izoket retard 20 – 2-3: 1 tablet per day;
  • Izoket retard 40 – 2 x 1 tablet per day;
  • Izoket retard 60 – 1 tablet per day or 2 times 1 tablet a day;
  • Izoket retard 120 – 1 capsule per day (preferably in the morning).

Izoket retard should be taken after meals, with liquid squeezed small amount of liquid.

When assigning more than one pill a day, the second tablet can be taken only 8 hours after the first to ensure the full effect of the drug (prevention of nitrate tolerance).

It is necessary to select a dose according to the individual needs of the patient in consultation with a physician. Symptoms of vascular collapse may occur after the first dose in patients with labile circulation.It may also be nitrate headache. The masteron hair loss appearance of both symptoms can be avoided if you start receiving treatment with half a tablet twice a day, t. E. With the lowest recommended dose.

WARNINGS:

The drug should not be taken in the first three months of pregnancy without a doctor’s recommendation.

  • Izoket not suitable for the treatment of acute attacks of angina.
  • Keep Izoket retard at a temperature no higher than 25 ° C.
  • The drug should not be used beyond the expiration date.

Store this medication out of reach of children!

PACKAGING AND PACKING:

  • Izoket retard 20, 40 or 60 – packing 20, 50 and 100 tablets.
  • Izoket retard 120 – packing 20, 50 and 100 capsules.

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masteron propionate

Posted on 08/24/2016  in Articles

Effect on serum gastrin: clinical trials in patients received rabeprazole at 10 or 20 mg once a day for up to 43 months.Serum gastrin concentration increased during the first 2-8 weeks of receiving, reflecting the inhibitory effect on the secretion of hydrochloric acid and then remained stable with continued therapy. Indicators masteron propionate gastrin concentrations returned to baseline values typically within 1-2 weeks after discontinuation of therapy.
Biopsy samples of antral stomach and bottom, obtained in more than 500 patients receiving rabeprazole or comparative treatment for up to 8 weeks showed no change in the ECL -kletochnom and histological structure, the degree of gastritis, incidence of atrophic gastritis, intestinal metaplasia or the prevalence of infection with H. pylori in more than 250 patients followed for 36 months of therapy, there was no significant change in baseline of existing conditions.

Other effects: systemic effect and rabeprazole in relation to the central nervous system, cardiovascular and respiratory systems are not identified to date. Rabeprazole, is applied orally at a dose of 20 mg for 2 weeks, had no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone (FSH), luteinizing hormone (LH), renin, aldosterone or growth hormone.
Clinical studies have shown that rabeprazole does not enter into a clinically significant interaction with amoxicillin, no adverse effect on the plasma concentrations of amoxicillin or clarithromycin, while the use of these drugs for eradication of H. pylori from the upper sections gastrointestinal tract.

Absorption: drug  is rabeprazole tablets, enteric-coated (gastric resistant) shell. This form is due to instability in the acidic environment of rabeprazole. Therefore, rabeprazole absorption begins only after the tablet has exited the stomach. Rapid absorption; the maximum concentration (C max ) of rabeprazole in plasma is reached after about 3.5 hours after ingestion of 20 mg. C max and AUC “concentration-time» (AUC) are linear over a dose range from 10 mg to 40 mg. The absolute bioavailability of an oral dose of 20 mg (as compared to intravenous administration) is about 52%, mostly due to presystemic metabolism. Repeated application of the bioavailability, presumably, does masteron propionate not increase. In healthy individuals, the half-life (Tu,) from the blood plasma of about 1 hour (from 0.7 to 1.5 hours), a total clearance – 283 ± 98 ml / min. Clinically significant interaction associated with eating there. Neither food nor the time of reception of the drug does not affect the absorption of rabeprazole.

 

Sex: taking into account the corrections for the growth and body weight showed no sex differences in the pharmacokinetic parameters of rabeprazole 20 mg.

Renal impairment: in patients with renal failure requiring hemodialysis (creatinine clearance (CC) of less than 5 mL / min / 1.73 m 2 ) of rabeprazole distribution was similar to its distribution in healthy volunteers. AUC and C max in these patients was about 35% lower than the corresponding parameters in healthy volunteers. Average T 1/2 , rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients on background hemodialysis and 3.6 hours – after hemodialysis. QC rabeprazole in patients with impaired renal function, requiring maintenance hemodialysis was approximately two times higher than in healthy volunteers.

Abnormal liver function: after a single application of rabeprazole 20mg patients with light or moderate liver disease 2 times increased AUC, and 2-3 times increased T 1/2 , rabeprazole compared with healthy volunteers. However, after oral administration of daily doses of 20 mg in 7 days only AUC increased 1.5 times, and C max – 1.2 times only. Tu, rabeprazole in patients with hepatic impairment was 12.3 hours compared to 2.1 chu healthy volunteers. The pharmacodynamic response (gastric pH control) in the two groups was clinically comparable.

Elderly patients: elderly patients slightly reduced excretion of rabeprazole. After application of rabeprazole for 7 days at a daily dose of 20 mg AUC increased approximately two-fold, and C max is increased by 60%, T 1.2 was increased by 30% as compared with healthy young volunteers. No signs of accumulation were observed rabeprazole. Polymorphism CYP2C19: rabeprazole after oral administration at a dose of 20 mg in humans sustained CYP2C19 – metabolism AUC and T 1/2 are approximately 1.9 and 1.6 times higher than the corresponding parameters in patients with active metabolism, while C max It increased by only 40%.

Indications

  • Gastric ulcer and duodenal ulcer in the acute stage;
  • Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (healing), symptomatic treatment of GERD, including long-term maintenance therapy;
  • Zollinger-Ellison syndrome;
  • In the combined therapy: the eradication of Helicobacter pylori in patients with gastric ulcer and 12 duodenal ulcer and chronic gastritis;
  • Treatment and prevention of relapse of peptic ulcer associated with Helicobacter pylori.

Contraindications

Hypersensitivity to the active substance or auxiliary components of the drug, pregnancy, breast-feeding, child age (no application experience).

Carefully

Severe renal impairment.

Application of pregnancy and during breastfeeding

Pregnancy
There are no data on the safety of rabeprazole in human pregnancy. Reproductive studies in rats and rabbits revealed no evidence of impaired fertility or harmful effects on the fetus of rabeprazole.
The drug Zulbeks not used during pregnancy.

Lactation
It is not known whether rabeprazole secreted in breast milk, but is secreted in the milk of rats. Studies in lactating women have not been conducted.
If necessary, use Zulbeks during lactation, breast-feeding should be discontinued.

Dosing and Administration

Inside, the whole without chewing and without breaking.

Peptic ulcer and 12 duodenal ulcer in the acute stage
of 20 mg 1 time a day, in the morning.
In most patients, active ulcer 12 duodenal ulcer heal within four weeks. However, some patients may need 4 more weeks for complete healing of the ulcer. Active benign gastric ulcer healing in most patients within six weeks. However, a small number of patients still six weeks may be required for complete healing.

Gastroesophageal reflux disease (GERD): erosive reflux esophagitis (healing), symptomatic treatment of GERD is
20 mg 1 time a day for four to eight weeks. Prolonged therapy Zulbeks maintenance dose preparation may be used – 10-20 mg once a day, depending on the patient’s response to treatment.

Symptomatic treatment of GERD:
10 mg 1 once daily in patients without esophagitis. If 4 weeks fails to achieve control of symptoms, it is necessary to conduct further examination of the patient. After the improvement of the patient’s condition further symptom control can be carried out while taking 10 mg 1 time per day, on request.

Zollinger-Ellison Syndrome
The recommended starting dose for adults is 60 mg 1 time per day. The dose may be increased to 120 mg a day depending on the individual patient’s needs. You can assign a daily dose of 100 mg 1 time per day. The dose of 120 mg six times may require acceptance, 60 mg 2 times a day. The therapy is carried out as long as there are appropriate clinical indications.

Eradication of H. pylori in patients with gastric ulcer and 12 duodenal ulcer or chronic gastritis:
patients with AN pylor, should undergo eradication therapy. We recommend the following combination regimens course 7 days: ® drug Zulbeks 20 mg 2 times daily + clarithromycin 500 mg 2 times daily and amoxicillin 1 g, 2 times a day.
If eradication schemes require masteron propionate the use of drugs 1 time per day, Zulbeks drug must taken in the morning before breakfast; time and food intake does not affect the activity of rabeprazole.

Renal dysfunction and / or hepatic impairment:
dosage adjustment Zulbeks preparation is required.

Children’s age: due to the lack of efficacy and safety data rabeprazole drug Zulbeks not used in children.

Side effect

Classification of the incidence of side effects of the World Health Organization (WHO):
very common> 1/10
often by> 1/100 to <1/10
uncommon from> 1/1000 to <1/100
rarely from> 1/10000 to <1 / 1000
is very rare on the <1/10000, including isolated reports.

In each group, adverse events are listed in order of decreasing seriousness.

From hemopoiesis system:
-rare: neutropenia, leukopenia, thrombocytopenia, leukocytosis, the part of the immune system: -rare: hypersensitivity reactions 1 , metabolic disorders and nutrition: -rare: anorexia, weight gain; Very rare: gnponatriemiya; Co nervous system: -Frequently: headache, dizziness, insomnia, -nechasto: drowsiness, nervousness; -rare depression; Very rare: confusion; From the senses: -rare: visual disturbances,cardio – vascular system : Very rare: peripheral edema; The respiratory system: -Frequently: cough, pharyngitis, rhinitis, -nechasto: bronchitis, sinusitis, part of the digestive system: -Frequently: diarrhea, vomiting, nausea, abdominal pain, constipation, flatulence ; -nechasto: dyspepsia, dry oral mucosa, belching; -rare: gastritis, stomatitis, changes in taste, hepatitis, jaundice, hepatic encephalopathy 3 ; For the skin: -nechasto: rash, erythema; -rare: itching, sweating , bullous rash 2 – very rare: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, the part of the musculoskeletal system:-Frequently: nonspecific pain, back pain; -nechasto: myalgia, leg cramps, arthralgia, From the urinary system: -nechasto: urinary tract infection; -rare: interstitial nephritis reproductive system: Very rare: gynecomastia; Laboratory findings: -nechasto: increased activity of liver enzymes Other: -Frequently: asthenia, flu-like illness. bodybuilding supplements uk

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steroid masteron

Posted on 08/24/2016  in Articles

Prevention and elimination of nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy, and postoperative nausea and vomiting.Hypersensitivity to any component of the drug, pregnancy and lactation.Children under 2 years (safety and efficacy has not been studied)

Choice dosage regimen is determined by the emetogenic anticancer therapy. For steroid masteron adults, the daily dose usually is 8-32 mg are recommended the following modes. For moderate emetogenic chemotherapy or radiotherapy:

  • 8 mg of ondansetron for 1-2 hours prior to the primary therapy, followed by taking further 8 hours after 12 mg.

When vysokoemetogennoy chemotherapy: The recommended dose is 24 mg in conjunction with dexamethasone sodium phosphate orally at a dose of 12 mg 1-2 hours before the start of chemotherapy.
For the prevention of late or prolonged vomiting occurring within 24 hours, you should continue taking  syrup at a dose of 8 mg two once a day for 5 days. Children  usually administered as a single solution for intravenous injection immediately before chemotherapy, followed by ingestion of a dose of 4 mg every 12 hours. After completion of chemotherapy is necessary to continue taking the syrup Zofran 4 mg twice a day for 5 days. Nausea and vomiting in the postoperative period Adults For the prevention of nausea and vomiting in postoperative period, we recommend taking 16 mg steroid masteron inside 1 hour prior to anesthesia. For relief posleperatsionnoy nausea and vomiting is used  injection. Children for the prevention and treatment of postoperative nausea and vomiting in children Zofran is administered as an intravenous injection. Elderly patients dosage change is required. Patients with renal insufficiency No special dosage changes receive frequencies or route of administration. Patients with hepatic impairment The daily dose of ondansetron should not exceed 8 mg per day. Patients with slow metabolism of sparteine / debrisokvina. Correction of daily dosage or frequency of administration of ondansetron are required.

Side effects: Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis. From the digestive system: hiccups, dry mouth, and constipation or diarrhea, sometimes asymptomatic transient increase in liver tests. Since the cardiovascular system: chest pain in some cases with ST-segment depression, arrhythmia, bradycardia, decreased blood pressure. from the nervous system:headache, dizziness, spontaneous movement disorders and seizures. Other: facial flushing, burning sensation, temporary disruption of visual acuity, gipoka- Liem, hypercreatininemia.

Overdose
There is limited experience of ondansetron overdose. In most cases, the symptoms are similar to the side effects of using the drug at the recommended doses. Treatment: the specific antidote for  not therefore recommended symptomatic and supportive therapy for suspected overdose. Use Zofran ipecac should not be an overdose, as its effectiveness is unlikely due to the anti-emetic action of .

Interaction with other drugs
There is no evidence that ondansetron induces or inhibits the metabolism of other drugs commonly prescribed in combination with it.
Ondansetron is metabolized by several cytochrome P450 enzyme system (CYP3A4, CYP2D6 and CYP1A2). Inhibition or reduction of activity of an enzyme is typically compensated by other normal, due to the significant decrease than the total clearance of ondansetron unlikely. Nevertheless, caution is required when used together:

  • P450 enzyme-inducers (of CYP2D6 and of CYP3A) (barbiturates, karbamaze-ping, carisoprodol, glutetimid, griseofulvin, nitrous oxide, papaverine, phenylbutazone steroid masteron, phenytoin (probably other hydantoins), rifampicin, tolbutamide);
  • with inhibitors of P450 enzymes (CYP2D6 and CYP3A) (allopurinol, macrolide antibiotics, antidepressants – MAO inhibitors, chloramphenicol, cimetidine, peroral-WIDE contraceptives containing estrogen, diltiazem, disulfiram, valproic acid, sodium valproate, erythromycin, fluconazole, fluoroquinolones, isoniazid, ketoko-Nazol, lovastatin, metronidazole, omeprazole, propranolol, quinidine, quinine, verapamil).

Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, tramadol and propofol (Diprivan).

 

Cautions
noted allergic reaction to  steroid masteron ondansetron in patients with a history of hypersensitivity to other antagonists of the 5HT 3 receptor.
Since ondansetron increases the passage of the contents on the large intestine, patients with signs of intestinal obstruction after treatment require regular monitoring.
Tablets for sucking contain aspartame, and therefore they should be used with caution in patients with phenylketonuria.
Tablets for resorption should not be squeezed out of the foil. The tablets from the packaging should take immediately before use.

Composition
Tablets for sucking 4 mg and 8 mg. 10 tablets in a blister pack of the five-layer laminate of aluminum / PVC foil. 1 blister with instructions for use in a carton box.

Shelf life
3 years.
Do not use after the expiration date printed on the package.

Storage conditions
List B. The temperature is below 30 ° C out of reach of children.

masteron cycle

Posted on 08/24/2016  in Articles

Prevention and elimination of nausea and vomiting induced by cytotoxic chemotherapy or radiotherapy, and postoperative nausea and vomiting.

Hypersensitivity masteron cycle to any component of the drug, pregnancy and lactation.Children under 2 years (safety and efficacy has not been studied)

Dosage and administration: Nausea and vomiting with cytotoxic chemotherapy or radiotherapy Choice dosage regimen is determined by the emetogenic anticancer therapy. For adults, the daily dose usually is 8-32 mg are recommended the following modes. For moderate emetogenic chemotherapy or radiotherapy:

8 mg of ondansetron for 1-2 hours prior to the primary therapy, followed by taking further 8 hours after 12 mg.

When vysokoemetogennoy chemotherapy: The recommended dose is 24 mg in conjunction with dexamethasone sodium phosphate orally at a dose of 12 mg 1-2 hours before the start of chemotherapy.
For the prevention of late or prolonged vomiting occurring within 24 hours, you should continue taking Zofran syrup at a dose of 8 mg two once a day for 5 days. Children Zofran usually administered as a single solution for intravenous injection immediately before chemotherapy, followed by ingestion of a dose of 4 mg every 12 hours. After completion of chemotherapy is necessary to continue taking the syrup Zofran 4 mg twice a day for 5 days. Nausea and vomiting in the postoperative period Adults For the prevention of nausea and vomiting in postoperative period, we recommend taking 16 mg masteron cycle inside 1 hour prior to anesthesia. For relief posleperatsionnoy nausea and vomiting is used Zofran injection. Children for the prevention and treatment of postoperative nausea and vomiting in children is administered as an intravenous injection. Elderly patients dosage change is required. Patients with renal insufficiency No special dosage changes receive frequencies or route of administration. Patients with hepatic impairment The daily dose of ondansetron should not exceed 8 mg per day. Patients with slow metabolism of sparteine / debrisokvina. Correction of daily dosage or frequency of administration of ondansetron are required.

Side effects: Allergic reactions: urticaria, bronchospasm, laryngospasm, angioedema, anaphylaxis. From the digestive system: hiccups, dry mouth, and constipation or diarrhea, sometimes asymptomatic transient increase in liver tests. Since the cardiovascular system: chest pain in some cases with ST-segment depression, arrhythmia, bradycardia, decreased blood pressure. from the nervous system:headache, dizziness, spontaneous movement disorders and seizures. Other: facial flushing, burning sensation, temporary disruption of visual acuity, gipoka- Liem, hypercreatininemia.

Overdose
There is limited experience of ondansetron overdose. In most cases, the symptoms are similar to the side effects of using the drug at the recommended doses. Treatment: the specific antidote for Zofran not therefore recommended symptomatic and supportive therapy for suspected overdose. Use  ipecac should not be an overdose, as its effectiveness is unlikely due to the anti-emetic action of masteron cycle.

Interaction with other drugs
There is no evidence that ondansetron induces or inhibits the metabolism of other drugs commonly prescribed in combination with it.
Ondansetron is metabolized by several cytochrome P450 enzyme system. Inhibition or reduction of activity of an enzyme is typically compensated by other normal, due to the significant decrease than the total clearance of ondansetron unlikely. Nevertheless, caution is required when used together.

Special studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, tramadol and propofol (Diprivan).

Cautions
noted allergic reaction to ondansetron in patients with a history of hypersensitivity to other antagonists of the 5HT 3 receptor.
Since ondansetron increases the passage of the contents on the large intestine, patients with signs of intestinal obstruction after treatment require regular monitoring.
Tablets for sucking contain aspartame, and therefore they should be used with caution in patients with phenylketonuria.
Tablets for resorption should not be squeezed out of the foil. The tablets from the packaging should take immediately before use.

Composition
Tablets for sucking 4 mg and 8 mg. 10 tablets in a blister pack of the five-layer laminate of aluminum / PVC foil. 1 blister with instructions for use in a carton box.

Shelf life
3 years.
Do not use after the expiration date printed on the package.

Storage conditions
List B. The temperature is below 30 ° C out of reach of children. how much to inject for weight loss

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masteron side effects

Posted on 08/24/2016  in Articles

 

 

If symptoms persist, or recur within 24 hours, you may need to receive booster dose . If the second dose is required, it must not be taken within 2 hours after the first dose. If the masteron side effects patient does not experience sufficient relief after 2.5 mg doses, subsequent migraine attacks may be treated  at a dose of 5 mg.A significant effect is apparent within 1 hour after receiving the . “The effectiveness of does not depend on how long after the beginning of the attack was taking the pill, but it is recommended to take  as soon as possible after the onset of migraine headache.In case of repeated attacks, it is recommended that the total dose to , adopted within 24 hours should not exceed 15 mg.

 

Masteron side effects  has a marked effect in migraine with aura and without aura and migraine associated with menstruation. The effectiveness of masteron side effects is not influenced by gender and age of the patient, the duration of the attack, the presence masteron side effects of nausea before taking this medication and the use of conventional drugs for the prevention of migraine attacks.

Use in children

Safety and efficacy of ‘Zomig’ in children is not established.

Apply in elderly

Safety and efficacy of ‘Zomig’ in people older than 65 years have not been systematically studied.

Patients with impaired hepatic function

No data from clinical or pharmacokinetic studies in patients with hepatic impairment treated with ‘Zomig’.

Patients with impaired renal function

No dose adjustment is required. (See section Pharmacokinetic properties).

CONTRAINDICATIONS

‘Zomig’ is contraindicated in patients with known hypersensitivity to the drug or any of its components.

‘Zomig’ should not be given to patients with uncontrolled hypertension.

WARNINGS AND PRECAUTIONS

‘Zomig’ should only be used if the diagnosis of “migraine” is clearly established. It is necessary to exclude other potentially serious neurological conditions. No data on the use of ‘Zomig’ with hemiplegic or basilar migraine.

‘Zomig’ should not be given to patients with symptomatic Wolff-Parkinson-White syndrome or arrhythmias associated with other additional ways of.

This class of drugs (5-HT 1D agonists) can cause narrowing of the coronary vessels, so patients with coronary heart disease were not included in clinical trials. For this reason “Zomig” not recommended for this group of patients. Patients with a probability of presence of unrecognized coronary artery disease is recommended to conduct a survey of cardiovascular therapy before 5HT 1D agonists.

As in the case of other 5HT 1D agonist zolmitriptan after administration abnormal sensations reported in the heart, however, in clinical trials it was not associated with arrhythmias or ischemic ECG changes.

‘Zomig’ could cause slight transient increase in blood pressure (which may be more pronounced in the elderly), but, in clinical trials it did not cause any impact.

Interactions with other drugs and other forms of interaction

There is no data confirming that the concomitant administration of drugs for the prevention of migraine (for example beta blockers, dihydroergotamine, pizotifen) has any effect on the efficacy or unwanted effects ‘Zomig’.

The pharmacokinetics and tolerability of ‘Zomig’ were not affected by the urgent cimptomaticheskogo treatment of migraine drugs such as paracetamol, metoclopramide and ergotamine. Concomitant administration of other 5HT 1D agonists within 12 hours after receiving the ‘Zomig “should be deleted.

After administration of moclobemide (inhibitor of MAO-A) has been a slight increase (by 2-6%) AUC for zolmitriptan and a three-fold increase in AUC for the active metabolite. Therefore, the maximum daily dose of ‘Zomig’ to patients taking MAO-A inhibitors, should not exceed 7.5 mg.

Pregnancy and lactation

Pregnancy

Pregnant women can apply “Zomig” only if the benefits to the mother justify the potential risk to the fetus. Studies in pregnant women have not been conducted, but there is no evidence of teratogenic properties of ‘Zomig’ for the results of studies in animals.

Lactation

Studies have shown that zolmitriptan penetrates into milk of lactating animals. No data on the penetration of zolmitriptan into human breast milk. Therefore, caution should be used for the appointment of ‘Zomig’ to women who are breastfeeding.

Effects on ability to drive and use other mechanisms

No significant deterioration in the performance of psychomotor tests at reception “Zomig” at a dose of 20 mg. It is unlikely that the use of ‘Zomig’ lead to deterioration of the patient’s ability to drive a car or other mechanisms. However, we must take into account the possibility of somnolence.

POSSIBLE ADVERSE REACTIONS

‘Zomig’ is well tolerated. Adverse reactions are usually mild / moderate, transient, not serious and resolve spontaneously without treatment.

Possible adverse reactions tend to occur within 4 hours after ingestion, and not more frequent with taking repeated doses.

The most frequently reported to the following adverse reactions:

Nausea, dizziness, somnolence, warm sensation, fatigue, dry mouth.

Just to report violations of sensitivity: possible feeling of heaviness and tightness in the throat, neck, limbs, and breast (in the absence of ischemic changes on ECG). It is also possible myalgia, muscle weakness, paresthesia and dysesthesia.

OVERDOSE

In volunteers who received a single dose of 50 mg orally, usually marked sedation. The half-life of zolmitriptan tablets 2.5 -3 hours (see. Section Pharmacokinetic properties), so in case of overdose, patients monitoring should continue for at least 15 hours or until there are symptoms of overdose.

For zolmitriptan is no specific antidote. In the case of severe intoxication recommended measures intensive care, including the establishment and maintenance of a patient airway patency, ensuring adequate oxygenation and ventilation, as well as the monitoring and support of the cardiovascular system.

It is not known what kind of effect on serum concentration of zolmitriptan having hemodialysis and peritoneal dialysis.

Pharmacological properties

Pharmacodynamic properties

In preclinical studies, “Zomig” demonstrated the properties of recombinant receptor selective agonist of 5-HT 1D type alpha and beta human vascular receptors. Zolmitriptan is a high affinity agonist towards 5HT 1D receptor with moderate affinity to 5HT 1A receptors. Zolmitriptan has no significant affinity (based on radioligand binding assays) or pharmacological activity towards the 5HT 2 , 5HT 3 , 5HT 4 , alpha 1-, alpha 2 -, beta 1 – adrenergic receptors, H 1 – and H 2 histamine receptors, muscarinic receptors, dopaminergic receptors type 1 and 2.

It is known that the sensitivity to the pain of the skull cavity structures are the blood vessels and the vessels of the dura mater. These tissues are innervated by afferent fibers of the trigeminal nerve. In animal experiments, administration of zolmitriptan caused, due to its agonist properties 5HT 1D receptor vessels, vasoconstriction associated with the suppression of the release of the peptide, calcitonin gene-related (CGRP), vasoactive intestinal peptide (VIP), and substance P. These two effects ( vasoconstriction and inhibition of the release of neuropeptides) are supposed to cause relief from the migraine attack, in particular, reduction of pain intensity within 1 hour after administration of the drug and reduce nausea, vomiting, photophobia and phonophobia associated with migraine.

In addition to peripheral action has an effect on zolmitriptan brainstem centers associated with migraine, which explains a second stable effect in the treatment of several series of migraine attacks in one patient. When migraine attack marked vasodilatation through the activation of reflex excitation supported orthodromic fibers of the trigeminal nerve and parasympathetic innervation of cerebral circulation through the release of the VIP, as the main effector transmitter. Zolmitriptan blocks this reflex stimulation and release of VIP.

Pharmacokinetics

After ingestion zolmitriptan rapidly and well absorbed (at least 64%). The mean absolute bioavailability of the parent substance – about 40%. It has an active metabolite (183S91, N–desmetil metabolite) which also possesses 5HT agonist activity to 1D receptors, but are 2-6 times higher than zolmitriptan (according to experiments on animals).

In healthy subjects of reception at a single dose, zolmitriptan and its active metabolite 183S91 have proportionally dependent on the dose AUC and C max in the dose range from 2.5 to 50 mg.

Absorption is fast. 75% of the C max is achieved within 1 hour and the plasma concentration is maintained for a subsequent 4-6 hours. Absorption of zolmitriptan is independent of food intake. When receiving multiple doses of drug accumulation was observed.

Zolmitriptan is eliminated mainly by hepatic biotransformation followed by isolation of the metabolites in urine. There are three main metabolites: indole-acetic acid (the major metabolite in plasma and urine), N-oxide and N – desmethyl analogues. N – desmetilirovanny metabolite (183S91) is an active metabolite and two others – are inactive. 183S91 plasma concentration is approximately half of the concentration of the parent substance, and therefore it can be assumed that this metabolite contributes to therapeutic effect ‘Zomig. ” More than 60% of the drug administered as a single oral dose is excreted in the urine (preferably in the form of indole-acetic metabolite) and about 30% excreted in feces mainly as unchanged parent compound.

After intravenous administration, the average total plasma clearance of 10 ml / min / kg, which is one third of renal clearance. Renal clearance is higher than the glomerular filtration, which implies the existence of tubular secretion. Volume distributions following intravenous administration – 2.4 l / kg. Binding to plasma proteins is low (about 25%). The average half-life of zolmitriptan 2.5-3 hours. The half-life of its metabolites is about the same, which involves removing as they are formed.

Renal clearance of zolmitriptan and its metabolites is reduced (7-8 fold) in patients with moderate to severe renal impairment as compared to healthy subjects of, although a Parent substance and AUC of the active metabolite were increased only slightly (16% and 35%, respectively) with increasing half-life at 1 hr (3-3.5 hours). These parameters were within the values observed in healthy volunteers.

According to a study on a small group of volunteers were observed pharmacokinetic interaction with ergotamine. Simultaneous administration “Zomig” with ergotamine / caffeine was well tolerated and did not lead to an increase in the frequency of adverse reactions or changes in blood pressure compared with the introduction of only ‘Zomig’.

Selegiline (MAO-B inhibitor) and fluoxetine (selective serotonin reuptake inhibitor) have no effect on the pharmacokinetic parameters of zolmitriptan.

The pharmacokinetics of zolmitriptan in healthy elderly people similar to faramakokinetikoy in healthy young men.

Pharmacological properties Pharmacodynamics : The antimicrobial agent of a broad spectrum fluoroquinolone acts on the bacterial enzyme DNA gyrase, which provides supercoiling and thus the stability of bacterial DNA (DNA destabilization chains leads to their destruction). It has a bactericidal effect. It is active against microorganisms, producing beta-lactamase, and fast-growing atypical mycobacteria. Sensitive: Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Citrobacter, Klebsiella spp. (including Klebsiella pneumonia), Enterobacter spp., Hafnia, Proteus spp. (including Proteus mirabilis, Proteus vulgaris – indole-positive and indole-negative), Salmonella spp, Shigella spp. . (including Shigella sonnei), Yersinia enterocolitica, Campilobacter jejuni, Aeromonas hydrophila, Plesiomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticus, Haemophilus influenzae, Chlamydia spp., Legionella spp., Serratia spp., Providencia spp., Haemophilus ducreyi, Bordetella parapertussis, Bordetella .. pertussis, Moraxella catarrhalis, Propionibacterium acnes, Staphylococcus spp, Brucella spp different sensitivity to the drug have: Enterococcus faecalis, Streptococcus pyogenes, pneumoniae and viridans, Serratio marcescens, Pseudomonas aeruginosa, Acinetobacter, Mycoplasma hominis and pneumoniae, Mycobacterium tuberculosis, and Mycobacterium .. fortuim, Ureaplasma urealyticum, Clostridium perfringens, Corynebacterium spp, Helicobacter pylori, Listeria monocytogenes, Gardnerella vaginalis In most cases insensitive: Nocardia asteroides, anaerobic bacteria (e.g., Bacteroides spp, Peptococcus spp, Peptostreptococcus spp, Eubacterium spp,…. Fusobacterium spp., Clostridium difficile). He acts on Treponema pallidum. Pharmacokinetics : Absorption after oral administration is fast and complete (95%). Bioavailability – over 96%, bond to plasma proteins – 25%, the time to reach maximum concentration (TStah) Orally – 2.1 h, the maximum concentration (Cmax) after administration at a dose of 100 mg, 300 mg to 600 mg of 1, 3 , 4 and 6.9 mg / l and depends on the dose: after a single dose of 200 mg and 400 mg of it is 2.5 mg / ml and 5 ug / ml, respectively. Food can slow down the absorption, but has no significant effect on bioavailability. The apparent volume of distribution – 100 l. It consists of cells (white blood cells, alveolar macrophages), skin, soft tissues, bones, organs of the abdomen and pelvis, respiratory system, urine, saliva, bile, prostate secretion, well penetrates the blood-brain barrier, placental barrier, is secreted in human milk . Penetrates into the cerebrospinal fluid when the inflamed and non-inflamed meninges (14-60%). It is metabolized in the liver (approximately 5%) with the formation of N-oxide and ofloxacin dimetilofloksatsina. The half – 4.5-7 h (regardless of dose). Excreted by the kidneys – 75-90% (unchanged), about 4% – with bile. Extrarenal clearance -. Less than 20% after a single application of 200 mg in the urine is detected for 20-24 h in renal / hepatic insufficiency excretion may slow down.. Not accumulates. In hemodialysis removes 10-30% of the drug.

Indications
respiratory tract infections (bronchitis, pneumonia), upper respiratory tract (sinusitis, pharyngitis, otitis media, laryngitis), skin, soft tissues, bones, joints, infectious and inflammatory diseases of the abdominal cavity and biliary tract (with the exception of bacterial enteritis) , the kidneys (pyelonephritis), urinary tract (cystitis, urethritis), pelvic organs (endometritis, salpingitis, oophoritis, cervicitis, Options, prostatitis), genitals (coleitis, orchitis, epididymitis), gonorrhea masteron side effects, chlamydia; septicemia (only for / in the introduction), meningitis; prevention of infections in patients with impaired immune status (including neutropenia).

Contraindications:
Hypersensitivity, deficiency of glucose-6-phosphate dehydrogenase, epilepsy (including history), lowering the seizure threshold (including after craniocerebral trauma, stroke or inflammation in the central nervous system); age up to 18 years (not yet completed skeletal growth), pregnancy, lactation.

Be wary – cerebral atherosclerosis, cerebrovascular accidents (in history), chronic renal failure, organic lesions of the central nervous system.

Dosing and Administration
Inside. Doses are selected individually depending on the location and severity of the infection and the sensitivity of micro-organisms, the general condition of the patient, and liver and kidney function.
Adults – 200-800 mg per day, course of treatment – 7-10 days, the multiplicity of applications – 2 times day. Dose to 400 mg per day may be administered in one administration, preferably in the morning. In gonorrhea – 400 mg once daily.
In patients with impaired renal function (when creatinine clearance 50-20 ml / min), the single dose should be 50% of the average doses for the multiplicity of 2 times a day, or a full single dose is administered 1 time per day . When creatinine clearance less than 20 mL / min, single dose – 200 mg, then – 100 mg a day every other day.
In hemodialysis and peritoneal dialysis -. 100 mg every 24 hours maximum daily dose in hepatic impairment – 400 mg / day.
Tablets taken as a whole, drinking water before or during meals. Duration of treatment is determined by the sensitivity of the causative agent and the clinical picture; Treatment should continue for at least 3 days after the disappearance of symptoms and complete normalization of temperature. In the treatment of salmonellosis treatment – 7-8 days in uncomplicated urinary tract infections of the lower course of treatment – 3-5 days.

Side effects
From the digestive system: gastralgia, anorexia, nausea, vomiting, diarrhea, flatulence, abdominal pain, increased activity of “liver” transaminases, hyperbilirubinemia, cholestatic jaundice, pseudomembranous enterocolitis.
From the nervous system: headache, dizziness, lack of movement, tremors, convulsions, numbness and paresthesias of extremities, intense dreams, “nightmarish” dream, psychotic reactions, anxiety, state of arousal, phobias, depression, confusion, hallucinations, increased intracranial pressure.
From the musculoskeletal system: tendinitis, myalgia, arthralgia , tenosynovitis, tendon rupture.
From the sensory organs: impaired color vision, diplopia, disturbances of taste, smell, hearing and balance.
With the cardiovascular system: tachycardia, decreased blood pressure, vasculitis, collapse.
Allergic reactions: skin rash, itching, urticaria, hypersensitivity pneumonitis, allergic nephritis, eosinophilia, fever, angioedema, bronchoconstriction, Stevens-Johnson syndrome and toxic epidermal necrolysis, photosensitivity, multiform exudative erythema, anaphylactic shock.
For the skin: petechial hemorrhages (petechiae), dermatitis bullous hemorrhagic, papular rash with masteron side effects a crust, indicating the defeat of vessels (vasculitis).
from the side of hematopoiesis: leukopenia, agranulocytosis, anemia, thrombocytopenia, pancytopenia, hemolytic and aplastic anemia.
from the urinary system: acute interstitial nephritis, renal dysfunction, hypercreatininemia, elevated levels of urea.
Other: goiter, superinfection, hypoglycemia (in patients with diabetes), vaginitis.

Overdosing
Symptoms: dizziness, confusion, lethargy, disorientation, drowsiness, vomiting. Treatment: gastric lavage, symptomatic therapy. With hemodialysis removes 10 – 30% of the formulation.

The interaction with other drugs
Food, antacids containing A13 +, Ca2 +, Mg2 + or iron salts, reduce the absorption of ofloxacin, forming insoluble complexes (the time interval between administration of these drugs must be at least 2 hours).
Decreases theophylline clearance by 25% (the concomitant use should be reduced dose theophylline).
cimetidine, furosemide, methotrexate and drugs that block tubular secretion – increase the concentration of ofloxacin in plasma.
Increases concentration of glibenclamide in plasma.
When concomitantly with vitamin K antagonists is necessary to control blood coagulation.
in the appointment of non-steroidal anti preparty, derivatives nitroimidazole and methylxanthines increases the risk of neurotoxic effects.
When concomitant administration with corticosteroids increases the risk of tendon rupture, particularly in the elderly.
in the appointment of agents, alkalizing urine (carbonic anhydrase inhibitors, citrate, sodium bicarbonate), increases crystalluria risk and nephrotoxic effects.

Cautions :
It is not the drug of choice for pneumonia caused by pneumococcus. Not indicated in the treatment of acute tonsillitis.
It is not recommended to use more than 2 months, exposed to sunlight, ultraviolet radiation (mercury-quartz lamp, solarium).
In case of any side effects on the central nervous system, allergic reactions, pseudomembranous colitis requires removal of the drug . If pseudomembranous colitis, confirmed by colonoscopy and / or histologically demonstrated oral administration of vancomycin and metronidazole.
Rarely occurring tendinitis can lead to tendon rupture (predominantly Achilles tendon), particularly in elderly patients. In the event of signs of tendonitis, you should immediately discontinue treatment, to produce immobilization of the Achilles tendon and consult a podiatrist.
In the period of treatment should refrain from driving motor vehicles and activities potentially hazardous activities that require high concentration and psychomotor speed reactions, can not use ethanol.
In applying the drug to women is not recommended to use tampons, due to the increased risk of developing thrush.
The treatment possible worsening of myasthenia gravis, frequent attacks of porphyria in predisposed patients.
It may lead to false negative results when bacteriological diagnosis of tuberculosis (prevents the release of Mycobacterium tuberculosis).
in patients with impaired hepatic or renal function should be monitored plasma concentrations of ofloxacin. In severe renal and hepatic impairment increases the risk of toxic effects (dose adjustment is required).
Children applies only when the threat of life, taking into account the intended use and the potential risk of side effects, it is not possible to use other, less toxic drugs. The average daily intake in this case – 7.5 mg / kg, the maximum – 15 mg / kg.

Form release
tablets, film-coated, 200 and 400 mg.
1 blister pack contains 10 tablets of 200 mg.
1 blister contains 5 tablets of 400 mg.
1 blister in a cardboard box with instructions for use.

Storage conditions
List B. The temperature is not above 25 ° C. Keep out of the reach of children.

Shelf life
2 years. Do not use after the expiration date.

Conditions of supply of pharmacies
by prescription.

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