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Active Ingredient: Topiramate.

Topamax is used for treating seizures in certain patients.

Other names for this medication:
Bipomax, Epimaxan, Epiramat, Epitomax, Erravia, Letop, Neutop, Piramax, Symtopiram, Talopam, Tidian, Tiramat, Topamac, Topibrain, Topictal, Topiegis, Topifar, Topigen, Topilek, Topilep, Topilex, Topimark, Topimatil, Topimax, Topina, Topinmate, Topira-q, Topiragamma, Topiramat, Topiramato, Topiramatum, Topiramed, Topirat, Topirax, Topirol, Topistad, Toplep, Toprel, Toramat, Zidoxer.

Clinico-pharmacological group
Anticonvulsant drug

Pharmachologic effect
Antiepileptic drug belongs to the class of sulphamate-substituted monosaccharides.

Topiramate blocks sodium channels and suppresses the occurrence of repeated action potentials against the background of prolonged depolarization of the neuron membrane. Topiramate increases the activity of GABA (GABA) with respect to certain subtypes of GABA receptors (including GABAA receptors), and also modulates the activity of the GABAA receptors themselves, and prevents the kainate / AMPK sensitivity to be activated by the kainate (alpha-amino-3-hydroxy -5-methylisoxazole-4-propionic acid) glutamate receptors, does not affect the activity of NMDA in relation to the NMDA receptor subtype. These effects of the drug are dose-dependent at plasma concentrations of topiramate from 1 μmol to 200 μmol, with a minimum activity ranging from 1 μmol to 10 μmol.

In addition, topiramate inhibits the activity of some isoenzymes of carbonic anhydrase. In terms of the severity of this pharmacological effect, topiramate is significantly inferior to acetazolamide, a known inhibitor of carbonic anhydrase, therefore this activity of topiramate is not the main component of its antiepileptic activity.

Pharmacokinetics
Suction

After taking the drug inside topiramate is quickly and effectively absorbed from the gastrointestinal tract. Bioavailability is 81%. Eating does not have a clinically significant effect on the bioavailability of the drug.

Topramata pharmacokinetics is linear, plasma clearance remains constant, and AUC in the dose range from 100 mg to 400 mg increases in proportion to the dose.

After repeated ingestion in a dose of 100 mg 2 times / day, Cmax averages 6.76 µg / ml.

Distribution

Plasma protein binding is 13-17%.

After a single oral dose of up to 1200 mg, the average Vd is 0.55-0.8 l / kg. Vd value depends on gender. In women, values ​​are approximately 50% of the values ​​observed in men, which is associated with a higher content of adipose tissue in the body of women.

In patients with normal renal function, it may take 4 to 8 days to achieve an equilibrium.

Metabolism

After ingestion, about 20% of the dose is metabolized.

From the human plasma, urine and feces, 6 practically inactive metabolites were isolated and identified.

Removal

Topiramate (70%) and its metabolites are excreted mainly by the kidneys.

After ingestion of plasma clearance of the drug is 20-30 ml / min.

After repeated administration of the drug in 50 mg and 100 mg 2 times / day, the average T1 / 2 averaged 21 hours.

Pharmacokinetics in special clinical situations

The rate of elimination of topiramate by the kidneys depends on the function of the kidneys and does not depend on age.

In patients with impaired renal function of moderate and severe (CK ≤ 70 ml / min), the renal and plasma clearance of topiramate decreases, resulting in an increase in plasma Css of topiramate in blood plasma compared with patients with normal renal function. The time to Css topiramate in plasma in patients with moderate or severe impaired renal function is from 10 to 15 days. Patients with moderate to severe renal failure are recommended to use half of the recommended initial and maintenance dose.

In the elderly, not suffering from kidney disease, plasma clearance of topiramate does not change.

In patients receiving concomitant therapy with antiepileptic drugs that induce enzymes involved in the metabolism of drugs, topiramate metabolism increased by 50%.

Topiramate is effectively eliminated by hemodialysis. Prolonged hemodialysis can lead to a decrease in the concentration of topiramate in the blood below the amount required to maintain anticonvulsant activity. To avoid a rapid drop in plasma topiramate concentration during hemodialysis, it may be necessary to prescribe an additional dose of Topamax.

Dose adjustment should take into account:

1) duration of hemodialysis;

2) the amount of clearance of the used hemodialysis system;

3) effective renal clearance of topiramat in a dialysis patient.

Plasma clearance of topiramate is reduced by an average of 26% in patients with moderate to severe liver failure. Therefore, patients with hepatic insufficiency should use topiramate with caution.

In children under the age of 12, the pharmacokinetic parameters of topiramate as well as in adults receiving the drug as an adjunct therapy are linear, while its clearance does not depend on the dose, and Css in plasma increases in proportion to the dose increase. It should be borne in mind that in children the clearance of topiramata is increased, and its T1 / 2 is shorter. Therefore, at the same dose per 1 kg of body weight, plasma topiramate concentrations in children may be lower than in adults. In children, as in adults, antiepileptic drugs that induce hepatic enzymes, cause a decrease in the concentration of topiramate in the blood plasma.

Indications
Epilepsy:

  • as monotherapy in adults and children over 2 years of age with epilepsy (including in patients with newly diagnosed epilepsy);
  • as part of complex therapy in adults and children over 2 years old with partial or generalized tonic-clonic seizures, as well as for the treatment of seizures in the presence of Lennox-Gastaut syndrome.

Migraine:

  • prevention of migraine attacks in adults (the use of Topamax for the treatment of acute migraine attacks has not been studied).

Contraindications

  • children’s age up to 2 years;
  • Hypersensitivity to the drug.

It should be used with caution in case of renal or hepatic insufficiency, nephroluritiasis (including in the past or in the family history), with hypercalciuria.

Dosage
The drug is taken orally, regardless of the meal.

Capsules should be carefully opened, mix their contents with a small amount (about 1 teaspoon) of any soft food. This mixture should be swallowed immediately, without chewing. Do not store the drug mixed with food until the next dose. Capsules Topamax can be swallowed whole.

To achieve optimal control of epileptic seizures in adults and children, it is recommended to begin treatment with the use of the drug in low doses, followed by titration to an effective dose.

Capsules are intended for patients who have difficulty swallowing tablets (for example, in children and elderly patients).

Partial or generalized tonic-clonic seizures, as well as seizures against the background of Lennox-Gastaut syndrome.

Combined anticonvulsant therapy in adults. The minimum effective dose is 200 mg / day. Typically, the total daily dose ranges from 200 mg to 400 mg and is taken in 2 divided doses. Some patients may need to increase the daily dose to a maximum of 1600 mg. It is recommended to start treatment with a low dose, followed by gradual selection of an effective dose. Selection of the dose begins with 25-50 mg, taking them overnight for 1 week. In the future, at intervals of 1-2 weeks, the dose can be increased by 25-50 mg and take it in 2 doses. The selection of the dose should be guided by the clinical effect. In some patients, the effect can be achieved when taking the drug 1 time / day. To achieve the optimal effect of treatment with Topamax, it is not necessary to control its plasma concentration.

These dose recommendations apply to all adult patients, including elderly patients, in the absence of kidney disease.

Combined anticonvulsant therapy in children older than 2 years. The recommended total daily dose of Topamax as an additional therapy is from 5 to 9 mg / kg and is taken in 2 divided doses. Selection of the dose should be started with 25 mg (or less, based on the initial dose of 1 to 3 mg / kg / day) at night for 1 week. In the future, the dose can be increased with an interval of 1-2 weeks for 1-3 mg / kg and take it in 2 doses. The selection of the dose should be guided by the clinical effect. Daily dosages up to 30 mg / kg are usually well tolerated.

Epilepsy (including first diagnosed)

When canceling concomitant anticonvulsant drugs for the purpose of monotherapy with topiramate, it is necessary to consider the possible influence of this step on the frequency of seizures. In cases where there is no need to abruptly cancel concomitant anticonvulsant drugs for safety reasons, it is recommended to reduce their doses gradually, reducing the dose of concomitant anti-epileptic drugs by 1/3 every 2 weeks.

With the abolition of drugs that are inducers of liver microsomal enzymes, the concentration of topiramate in the blood will increase. In such situations, in the presence of clinical indications, the dose of Topamax can be reduced.

When monotherapy in adults at the beginning of treatment, Topamax is prescribed at a dose of 25 mg at bedtime for 1 week. Then the dose is increased with an interval of 1-2 weeks by 25 mg or 50 mg in 2 doses. If the patient does not tolerate such a mode of increasing the dose, you can increase the intervals between dose increases, or increase the dose more smoothly. The selection of the dose should be guided by the clinical effect. The initial dose for monotherapy with topiramate in adults is 100 mg / day, and the maximum daily dose should not exceed 500 mg. Some patients with refractory forms of epilepsy tolerate monotherapy with topiramate in doses up to 1000 mg / day. These dosing recommendations apply to all adults, including elderly patients without kidney disease.

When monotherapy for children over the age of 2 years in the first week of treatment, Topamax is prescribed at a dose of 0.5-1 mg / kg of body weight at bedtime. Then the dose is increased with an interval of 1-2 weeks by 0.5-1 mg / kg / day in 2 doses. If the child does not tolerate such a mode of increasing the dose, it is possible to increase the dose more smoothly or increase the intervals between dose increases. The magnitude of the dose and the rate of its increase depends on the clinical effect. The recommended dose range for monotherapy with topiramate in children over the age of 2 years is 100-400 mg / day. Children with newly diagnosed partial seizures can be given up to 500 mg / day.

Migraine

For the prevention of migraine attacks, the recommended daily dose of topiramate is 100 mg in 2 divided doses. At the beginning of treatment, 25 mg is prescribed at bedtime for 1 week. Then the dose is increased by 25 mg / day with an interval of 1 week. In case of intolerance to such a regimen of therapy, the dose is increased by a smaller amount or at long intervals. The dose is selected depending on the clinical effect. In some cases, a positive result is achieved with a daily dose of topiramate 50 mg. In clinical studies, patients received various doses of topiramate, but not more than 200 mg / day.

Special patient groups

Patients with moderate to severe renal insufficiency may need a dose reduction. The use of half the recommended initial and maintenance dose is recommended.

Hemodialysis: since topiramate is removed from plasma during hemodialysis, on the days of hemodialysis, an additional dose of Topamax should be administered, equal to about half the daily dose. The additional dose should be divided into two doses taken at the beginning and after completion of the hemodialysis procedure. The additional dose may vary depending on the characteristics of the equipment used during hemodialysis.

In patients with hepatic insufficiency, topiramate should be used with caution.

Side effects
Determination of the frequency of side effects: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10 000 and <1 / 1000) and very rarely (<1/10 000).

From the side of the central nervous system: very often – drowsiness, dizziness, paresthesias, in children – apathy, impaired attention; often – impaired motor coordination, nystagmus, lethargy, impaired memory, tremor, amnesia, abnormal gait, hypoesthesia, taste perversion, impaired thinking, cognitive disorders, apathy, mental decline, psychomotor disorders, sedative action; infrequently – loss of taste sensitivity, akinesia, loss of smell, aphasia, apraxia, aura, burning sensation in the limbs or on the face, cerebellar syndrome, circadian rhythm sleep disorder, complex partial seizures, convulsions, postural dizziness, dysesthesia, sensitivity disorder, dysography, dyskinesia , dysphasia, dystonia, tingling sensation in the body, tonic-clonic seizures of grand mal type, hyperesthesia, hypogemia, hypokinesia, hyposmia, peripheral neuropathy, parosmia, pre-fainting states, repetitive p To treat, violation of touch, stupor, fainting, lack of response to stimuli, in children – psychomotor hyperactivity.

Mental disorders: often – delayed thinking, pronounced speech disorders, confusion, depression, insomnia, aggressive reactions, agitation, disorientation, emotional lability, erectile dysfunction, in children – behavioral change, learning disability (difficulty reading, writing, counting); infrequently – anorgasmia, sexual dysfunction, tearfulness, disturbance of sexual arousal, dysfemia, early waking up in the morning, euphoric mood, auditory and visual hallucinations, hypomania states, decreased libido, mania, mania, panic state, paranoid states, thinking perseveration, misunderstandings, habits sleep, suicidal ideation or trying, crying; very rarely – a feeling of despair.

On the part of the digestive system: very often – reduction of appetite, anorexia; often – nausea, diarrhea; infrequently – abdominal pain, constipation, stomach discomfort, dyspepsia, dry mouth, impaired oral sensitivity, gastritis, gastroesophageal reflux, bleeding gums, heaviness in the stomach, in children – vomiting, unpleasant smell from the mouth, discomfort in the epigastric areas, flatulence, glossodynia, pain in the mouth, pancreatitis, salivary hypersecretion, thirst.

On the part of the musculoskeletal system: often – myalgia (including in the chest), muscle spasms, muscle cramps, arthralgia; infrequently – pain in the side, muscle fatigue, muscle weakness, muscle stiffness; very rarely – swelling of the joints, discomfort in the limbs.

Since the cardiovascular system: sometimes – bradycardia, rapid heartbeat, flushing, orthostatic hypotension, Raynaud’s phenomenon.

On the part of the organ of vision: often – diplopia, impaired vision, dry eyes; infrequently – disturbance of accommodation, amblyopia, blepharospasm, transient blindness, unilateral blindness, increased lacrimation, mydriasis, night blindness, photopsia, presbyopia, scotoma (including atrial), reduction of visual acuity; very rarely – discomfort in the eyes, angle-closure glaucoma, involuntary movements of the eyeballs, eyelid edema, myopia, maculopathy, conjunctival edema.

From the organ of hearing: often – pain in the ears, ringing in the ears, in children – vertigo; infrequently – deafness (including neurosensory and unilateral), discomfort in the ears, hearing impairment.

On the part of the respiratory system: often – difficulty breathing, nosebleeds; infrequently – hoarseness, shortness of breath on exertion, nasal congestion, hypersecretion in the paranasal sinuses, in children – rhinorrhea; very rarely – nasopharyngitis.

From the hemopoietic system: often – anemia; infrequently – leukopenia, lymphadenopathy, thrombocytopenia, in children – eosinophilia; very rarely – neutropenia.

On the part of the skin and subcutaneous tissues: often – a rash, alopecia, itching, decrease in the sensitivity of the skin of the face; infrequently – lack of sweating, allergic dermatitis, reddening of the skin, impaired skin pigmentation, swelling of the face, unpleasant skin odor, urticaria; very rarely – erythema multiforme, paraorbital edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system: often – nephrolithiasis, dysuria, pollakiuria; infrequently – exacerbation of urolithiasis, hematuria, urinary incontinence, frequent urination, renal colic, pain in the kidneys; very rarely – renal tubular acidosis.

From the laboratory indicators: infrequently – a decrease in the content of bicarbonate in the blood (on average by 4 mmol / l), crystalluria, leukopenia, hypokalemia (decrease in the level of potassium in the blood serum below 3.5 mmol / l).

General disorders: very often – fatigue, irritability, weight loss; often – asthenia, anxiety, in children – fever; infrequently – facial edema, allergic reactions, hyperchloremic acidosis, hypokalemia, increased appetite, metabolic acidosis, polydipsia, cold extremities, fatigue, weakness, calcification; very rarely – generalized edema, flu-like illness, angioedema, weight gain.

Overdose
Symptoms: convulsions, drowsiness, impaired speech and vision, diplopia, impaired thinking, impaired coordination, lethargy, stupor, arterial hypotension, abdominal pain, dizziness, agitation and depression. In most cases, the clinical consequences were not severe, but deaths were observed after an overdose using a mixture of several drugs, including topiramate. Perhaps the development of severe metabolic acidosis.

A case of overdose is known, when the patient took a dose of topiramate from 96 to 110 g, which caused a coma lasting for 20-24 hours. After 3-4 days, the symptoms of overdose resolved.

Treatment: if shortly before receiving an excessive dose of the drug, the patient took food, you must immediately flush the stomach or induce vomiting. In vitro studies have shown that activated carbon adsorbs topiramate. If necessary, symptomatic therapy should be carried out. An effective way to remove topiramate from the body is hemodialysis. Patients are recommended an adequate increase in fluid intake.

Drug interaction
Effect of Topamax on concentrations of other antiepileptic drugs (AEP)

Simultaneous administration of Topamax with other PEP (phenytoin, carbamazepine, valproic acid, phenobarbital, primidon) does not affect plasma Css values, except for certain patients in whom the addition of Topamax to phenytoin may cause an increase in plasma phenytoin concentration. This may be due to the inhibition of a specific polymorphic isoform of the cytochrome P450 enzyme system (CYP2Cmeph). Therefore, when symptoms of toxicity develop in patients receiving phenytoin, it is necessary to control the concentration of phenytoin in the blood plasma.

In the study of pharmacokinetics in patients with epilepsy, the addition of topiramate to lamotrigine did not affect the Css of the latter in plasma at doses of topiramate 100-400 mg / day. During and after the abolition of lamotrigine (the average dose of 327 mg / day), Css topiramate did not change.

The effect of other probes on the concentration of topiramate in plasma

Phenytoin and carbamazepine, while used with Topamax, reduce the concentration of topiramate in the plasma. Adding or removing phenytoin or carbamazepine during treatment with Topamax may require a dose change of the latter. The dose is selected depending on the development of the required clinical effect. Addition or removal of valproic acid does not cause clinically significant changes in the concentration of topiramate in the blood plasma and, therefore, does not require a change in the dose of Topamax.

In studies conducted with simultaneous use of the drug Topamax in a single dose of AUC of digoxin was reduced by 12%. The clinical significance of this effect has not been established. When prescribing or withdrawing the drug Topamax in patients receiving digoxin, it is necessary to monitor the concentration of digoxin in the serum.

As part of clinical studies, the effects of joint use of the drug Topamax with drugs that inhibit the function of the central nervous system, as well as with ethanol, have not been studied. The combined use of the drug Topamax with drugs that have a depressant effect on the central nervous system, and with ethanol is not recommended.

When co-administering Topamax and Hypericum perforatum preparations based on Hypericum perforatum, the concentration of topiramate in the plasma may decrease and, as a result, the effectiveness of the preparation may also decrease. Clinical studies of the interaction of the drug Topamax and preparations based on Hypericum perforatum have not been conducted.

With simultaneous use of an oral contraceptive containing norethisterone (1 mg) and ethinyl estradiol (35 mcg), Topamax in doses of 50-800 mg / day did not significantly affect the effectiveness of norethisterone and in doses of 50-200 mg / day – on the effectiveness of ethinyl estradiol. A significant dose-dependent decrease in the effectiveness of ethinyl estradiol was observed at doses of the drug Topamax 200-800 mg / day. The clinical significance of the described changes is not clear. The risk of reducing the effectiveness of contraceptives and enhancing breakthrough bleeding should be considered in patients taking oral contraceptives in combination with Topamax. Patients taking estrogen-containing contraceptives should inform the doctor about any changes in the timing and nature of menstruation. The effectiveness of contraceptives can be reduced even in the absence of breakthrough bleeding.

In healthy volunteers, lithium AUC decreased by 18% while taking topiramate at a dose of 200 mg / day. In patients with manic-depressive psychosis, the use of topiramate in doses up to 200 mg / day did not affect the pharmacokinetics of lithium, but at higher doses (up to 600 mg / day), lithium AUC was increased by 26%. With the simultaneous use of topiramate and lithium should monitor the concentration of the latter in the blood plasma.

Studies of drug interactions conducted with a single and multiple administration of topiramate to healthy volunteers and patients with manic-depressive psychosis, gave the same results. With the simultaneous use of topiratam in daily doses of 250 mg or 400 mg of AUC of risperidone taken in doses of 1-6 mg / day, reduced by 16% and 33%, respectively. At the same time, the pharmacokinetics of 9-hydroxyrisperidone did not change, and the total pharmacokinetics of the active substances (risperidone and 9-hydroxyrisperidone) changed insignificantly. Changes in the level of systemic exposure to risperidone / 9-hydroxyrisperidone and topiramate were not clinically significant, and this interaction is unlikely to have clinical significance.

Drug interactions were studied in healthy volunteers with separate and co-administration of hydrochlorothiazide (25 mg) and topiramate (96 mg). The research results showed that while taking topiramate and hydrochlorothiazide, there is an increase in Cmax of topiramate by 27% and its AUC by 29%. The clinical significance of these studies has not been identified. When administering hydrochlorothiazide to patients taking topiramate, dose adjustment of topiramate may be required. There were no significant changes in the pharmacokinetic parameters of hydrochlorothiazide with concomitant therapy with topiramate.

Drug interactions were studied in healthy volunteers who received metformin or a combination of metformin and topiramate. Research results showed that while taking topiramate and metformin, Cmax and AUC of metformin increased by 18% and 25%, respectively, while clearance of metformin and simultaneous administration with topiramate decreased by 20%. Topiramate had no effect on Tmax of metformin in the blood plasma. The clearance of a topiramat at joint appointment with metformin decreases. The degree of clearance changes have not been studied. The clinical significance of the effects of metformin on topiramate pharmacokinetics is not clear. In the case of the addition or withdrawal of the drug Topamax in patients receiving metformin, the condition of patients with diabetes should be monitored.

Drug interactions were studied in healthy volunteers with separate and co-administration of pioglitazone and topiramate. It was revealed a decrease in the AUC of pioglitazone by 15%, without changing the Cmax of the drug. These changes were not statistically significant. Also for the active hydroxymetabolite pioglitazone, a decrease in Cmax and AUC was detected by 13% and 16%, respectively, and for active ketometabolite, a decrease in both Cmax and AUC by 60% was found. The clinical significance of this data has not been elucidated. When patients are jointly prescribed Topamax and pioglitazone, the patient’s condition should be carefully monitored to assess the course of diabetes.

A study of drug interactions was conducted to study the pharmacokinetics of glibenclamide (5 mg / day) in an equilibrium state, used alone or simultaneously with topiramate (150 mg / day) in patients with type 2 diabetes. When using topiramate AUC glibenclamide was reduced by 25%. The level of systemic exposure to active metabolites, 4-trans-hydroxy-glibenclamide and 3-cis-hydroxy-glibenclamide, was also reduced (by 13% and 15%, respectively). Glibenclamide did not affect the pharmacokinetics of topiramate in equilibrium. A statistically insignificant decrease in the AUC of pioglitazone by 15% was found with no change in its Cmax. When administering topiramate to patients receiving glibenclamide (or prescribing glibenclamide to patients receiving topiramate), the patient’s condition should be carefully monitored to assess the course of diabetes.

With the simultaneous use of the drug Topamax with other drugs predisposing to the development of nephrolithiasis, it is possible to increase the risk of kidney stones. During the period of treatment with Topamax, the use of such drugs should be avoided, since they can cause physiological changes that contribute to the development of nephrolithiasis.

The combined use of topiramate and valproic acid in patients who tolerate each drug well separately is accompanied by hyperammonemia with or without encephalopathy. In most cases, the symptoms and signs disappear after the cancellation of one of the drugs. This adverse event is not caused by pharmacokinetic interaction. The relationship between hyperammonemia and the use of topiramate alone or in combination with other drugs has not been established.

When combined with topiramate and valproic acid, hypothermia may occur (unintended decrease in body temperature below 35 ° C) in combination with hyperammonemia or independently. This phenomenon can occur both after the start of joint administration of valproic acid and topiramate, and with an increase in the daily dose of topiramate.

Special instructions
Cancel Topamax (like other anti-epileptic drugs) should be gradually, to minimize the possibility of increasing the frequency of seizures. To reduce the dose by 25-50 mg, Topamax is used in the form of capsules in a dosage of 15 mg or 25 mg. In clinical studies, the dose of the drug was reduced by 50-100 mg 1 time per week – for adults with epilepsy therapy and 25-50 mg – for adults receiving Topamax at a dose of 100 mg / day for the prevention of migraine. In children in clinical studies, Topamax was gradually canceled over a period of 2-8 weeks. If, for medical reasons, rapid withdrawal of Topamax is necessary, then it is recommended that the patient be monitored accordingly.

As with any disease, the dosage regimen should be set in accordance with the clinical effect (i.e., the degree of seizure control, no side effects) and take into account the fact that in patients with impaired renal function to establish a stable plasma concentration for each dose need a longer time.

With topiramate therapy, oligohydrosis (reduced sweating) and anhidrosis can occur. Reduction of sweating and hyperthermia (increased body temperature) may occur in children exposed to high ambient temperatures. During therapy with topiramate, it is very important to adequately increase the volume of fluid consumed, which helps reduce the risk of developing nephrolithiasis, as well as side effects that may occur under the influence of physical exertion or elevated temperatures.

When treating with topiramate, there is an increased incidence of mood disorders and depression.

The use of antiepileptic drugs, including Topamax, increases the risk of suicidal thoughts and suicidal behavior in patients taking these drugs for any of the indications.

In double-blind clinical studies, the incidence of phenomena associated with suicide (suicidal thoughts, attempted suicide, suicide) was 0.5% in patients treated with topiramate (46 people out of 8652), which is about 3 times higher than in patients placebo (0.2%; 8 people out of 4045). One case of suicide was recorded in a double-blind study of bipolar disorder in a patient receiving topiramate.

Thus, it is necessary to monitor the condition of patients in order to identify signs of suicidal thoughts and prescribe appropriate treatment. Patients (and, if necessary, caregivers) should be advised to immediately seek medical attention if they show signs of suicidal thoughts or suicidal behavior.

Some patients, especially those with a predisposition to nephrolithiasis, may have an increased risk of kidney stones and associated symptoms, such as renal colic. To reduce this risk, an adequate increase in fluid intake is needed. Risk factors for nephrolithiasis are nephrolithiasis in history (including family), hypercalciuria, concomitant therapy with other drugs that contribute to the development of nephrolithiasis.

Caution must be exercised in the appointment of Topamax to patients with renal insufficiency (CC <70 ml / min). This is due to the fact that in such patients the clearance of the drug is lowered.

In patients with impaired liver function, Topamax should be used with caution because of a possible decrease in clearance of topiramate.

When using the drug Topamax described syndrome, including acute myopia with concomitant secondary angle-closure glaucoma. Symptoms include acute reduction of visual acuity and / or pain in the eye. Ophthalmologic examination may show myopia, flattening of the anterior chamber of the eye, hyperemia (redness) of the eyeball, and increased intraocular pressure. Mydriasis may occur. This syndrome may be accompanied by secretion of fluid, leading to the displacement of the lens and the iris forward with the development of secondary angle-closure glaucoma. Symptoms usually appear 1 month after starting Topamax. Unlike primary open-angle glaucoma, which is rarely seen in patients under 40 years of age, secondary angle-closure glaucoma is observed with the use of topiramate in both adults and children. In the event of a syndrome involving myopia associated with angle-closure glaucoma, treatment includes discontinuing Topamax as soon as the attending physician considers it possible, and appropriate measures aimed at lowering intraocular pressure. Usually these measures lead to the normalization of intraocular pressure.

Increased intraocular pressure of any etiology in the absence of adequate treatment can lead to serious complications, including loss of vision.

When using topiramate, hyperchloremic, not associated with anion deficiency, metabolic acidosis can occur (for example, a decrease in blood bicarbonate concentration by an average of 4 mmol / l in the absence of respiratory alkalosis). Such a decrease in serum bicarbonate concentration is a consequence of the inhibitory effect of topiramate on renal carbonic anhydrase. In most cases, a decrease in bicarbonate concentration occurs at the beginning of the drug intake, although this effect may occur during any period of treatment with topiramate. The level of reduction is usually mild or moderate (the average value is 4 mmol / l when used in adult patients at a dose of more than 100 mg / day and about 6 mg / kg / day when used in pediatric practice). In rare cases, patients had a decrease in concentration below 10 mmol / l. Some diseases or treatments that predispose to the development of acidosis (for example, kidney disease, severe respiratory diseases, status epilepticus, diarrhea, surgical interventions, ketogenic diet, taking certain medications) can be additional factors that enhance the bicarbonate-reducing effect of topiramate.

In children, chronic metabolic acidosis can lead to stunted growth. The effect of topiramate on growth and possible complications associated with the skeletal system have not been systematically studied in children and adults.

In connection with the foregoing, in the treatment with topiramate it is recommended to conduct the necessary studies, including the determination of the concentration of bicarbonate in serum. If metabolic acidosis occurs and persists, it is recommended to reduce the dose or stop taking Topamax.

If, against the background of taking the drug Topamax, the patient’s body weight decreases, then the question of the expediency of enhanced nutrition should be considered.

Laboratory values

Hypokalemia, defined as a decrease in serum potassium concentration below 3.5 mmol / l, was observed in 0.4% of patients receiving topiramate.

Influence on ability to drive motor transport and control mechanisms

Topamax acts on the central nervous system and may cause drowsiness, dizziness, blurred vision and other symptoms. These adverse effects can be dangerous for patients driving a car and moving machinery, especially during the period until the patient’s reaction to the drug is established.

Pregnancy and lactation
Special controlled studies in which Topamax was used to treat pregnant women have not been conducted. Pregnancy records show a possible link between the use of Topamax during pregnancy and congenital malformations (for example, craniofacial defects such as cleft lip / cleft palate, hypospadias and abnormalities in the development of various body systems). These malformations were recorded both in monotherapy with topiramate and in its use in the framework of polytherapy. Compared with the group of patients not taking antiepileptic drugs, the records of pregnancies with monotherapy with Topamax indicate the likelihood of the birth of children with low body weight (less than 2500 g). The relationship of the observed phenomena with the drug is not installed.

In addition, the records of pregnancies and the results of other studies suggest that the risk of teratogenic effects in the combined treatment of antiepileptic drugs may be higher than in monotherapy. Use of the drug Topamax during pregnancy is justified only in the case when the potential benefits of therapy for the mother outweigh the possible risk to the fetus.

When treating and consulting women with childbearing potential, the attending physician should weigh the ratio of benefits and risks of treatment and consider alternative treatment options. If Topamax is used during pregnancy, or if the patient became pregnant while taking this drug, it should be warned of the potential risk to the fetus.

A limited number of observations suggests that topiramate is excreted in breast milk in women. If necessary, the use of the drug Topamax during lactation should decide on the termination of breastfeeding.

Use in childhood
The drug is contraindicated for use in children under 2 years.

In case of impaired renal function
When prescribing the drug to patients with moderately or severely impaired renal function, it should be borne in mind that in order to achieve an equilibrium state in this category of patients, it may take 10-15 days, in contrast to 4-8 days in patients with normal renal function. Since topiramate is removed from plasma during hemodialysis, on the days of its holding, an additional dose of the drug equal to half the daily dose should be administered in 2 doses (before and after the procedure).

It should be used with caution in renal failure, nephroluritiasis (including in the past or in family history), and in hypercalciuria.

With abnormal liver function
Caution should be used when liver failure. In patients with moderately severe and severely impaired liver function, plasma clearance is reduced.

Terms and conditions of storage
The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25 ° C. Shelf life – 2 years.

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Other names for this medication:
Adifen, Adopan, Bagotam, Bilem, Bioxifeno, Citofen, Crisafeno, Doctamoxifene, Ebefen, Emalook, Femoxtal, Fenobest, Ginarsan, Gynatam, Mamofen, Neophedan, Nolgen, Nomafen, Norxifen, Novofen, Oncotamox, Panleef, Phenolurn, Puretam, Respol, Rolap, Tamec, Tamifen, Tamizam, Tamokadin, Tamona, Tamoneprin, Tamophar, Tamosin, Tamoxen, Tamoxene, Tamoxi, Tamoxifène, Tamoxin, Tamoxis, Tamoxistad, Tamsulon, Tasuomin, Taxfeno, Tecnotax, Trimetrox, Yacesal, Zymoplex.

Nolvadex
Active Ingredient: Tamoxifen
In 1 tablet tamoxifen citrate 10 or 20 mg

Pharmachologic effect
Antiestrogenic (prevents the formation of female sex hormones), antitumor.

Pharmacodynamics and pharmacokinetics
Pharmacodynamics

Nolvadex is a non-steroidal antagonist of estrogens. Specifically binds to estrogen receptors in peripheral and tumor tissues. Thus, eliminates the effect of estrogens produced in the body and stimulating the growth of cancer cells.

Slows the progression of the tumor process. After taking a single dose a few weeks will retain the ability to block estrogens. Causes ovulation in women, in men with oligospermia increases the level of LH and FSH.

Pharmacokinetics

When ingested quickly absorbed, and after 5-7 hours in the blood creates a maximum concentration. 99% is associated with blood proteins (albumin). Excretion takes place biphasic: initial T 1/2 from 8 to 14 h, final T 1/2 – 7 days. It is excreted with feces, only a small part with urine. Indications for use
Nolvadex is used when:

❀estrogen-dependent breast tumors in postmenopausal women;
❀endometrial cancer. Contraindications

Nolvadex tablets are contraindicated in:

❀hypersensitivity;
❀pregnancy;
❀breastfeeding;
❀cataract;
❀expressed thrombophlebitis;
❀leukopenia, thrombocytopenia.

Nolvadex can cause the following undesirable reactions:

❀dizziness;
❀gastrointestinal disorders and nausea;
❀uterine bleeding, endometrial hyperplasia, uterine fibroid, pruritus vulva;
❀fluid retention in the body;
❀hypercalcemia;
❀thrombocytopenia, leukopenia;
❀alopecia;
❀pain in the bones;
❀changes in the retina of the eye;
❀thromboembolism.

Instructions for use (Method and dosage)
Nolvadex pills are taken orally without chewing, with water. It is possible to take the whole dose at one time in the morning or for two meals – in the morning and in the evening. In breast cancer 20-40 mg is prescribed, with endometrial cancer 30-40 mg. The maximum SD is 40 mg. Treatment is carried out for a long time, often in combination with cytostatic and radiotherapy.

During the treatment period, blood coagulability, leukocytes, platelets, calcium level in the blood, liver function are controlled. The oculist is examined quarterly and gynecological examination. The drug Nolvadex is ineffective in the presence of metastases (especially in the liver). Overdose
It is manifested by increased side effects. Symptomatic treatment is performed. Antidote does not exist.
Nolvadex (Tamoxifen) enhances the effect of anticoagulants. Simultaneous reception of the drug with estrogen-containing contraceptives causes a decrease in the effect of both drugs.

Use with Tegafur can lead to hepatitis and cirrhosis of the liver. Allopurinol also enhances its hepatotoxic effect.

Joint reception with cytostatics significantly increases the risk of thrombosis.
Admission with diuretics of the thiazide series increases the risk of hypercalcemia.

H2-histamine receptor blockers and antacids can cause premature dissolution of the enteric-dissolving tablet, so the time between taking these drugs should be 2 hours.

Storage conditions
At temperatures up to 30C.

Shelf life
5 years.

Despite the fact that Tamoxifen has been used to treat and prevent the recurrence of breast cancer since 1998, it can now be considered a “gold standard” in the treatment of this disease. Nolvadex or its substitutes are still used today in oncology, which is confirmed by the reviews of patients who are prescribed this drug for a long time.

“They removed the right breast, after the course of radiation therapy they prescribed Tamoxifen for 5 years”

It was proved that the effectiveness of the drug increases with long-term admission and it was prescribed immediately for five years of constant admission. This reduces the mortality of patients after discontinuation and prolongs life for decades. Treatment with estrogen antagonists can prevent the possibility of tumor metastasis. After this period, the oncologist assesses the condition and draws conclusions: prolong treatment, add cytotoxic drugs or aromatase inhibitors.

According to some data, the drug is effective only in elderly women. After long-term administration of the drug, adverse reactions are reported, which patients report: pain in the hip, weight gain, hair loss, varicose veins and thrombophlebitis, itching.

The drug can be prescribed and for preventive purposes to prevent breast cancer in women who are predisposed to this disease. Specific data have been obtained that taking the drug reduces the risk of developing breast cancer by one third. However, an unexpected side effect is found – there is a risk of sarcoma of the uterus. On this issue, discussions are under way and clinical trials are continuing. When appointing Tamoxifen for prophylaxis, the doctor should discuss with the patient the benefit of the drug and the existing risk.

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Antibiotic Doxycycline☤ – a characteristic of the drug

Antibiotics of the tetracycline series, which include Doxycycline☤, have a wide spectrum of action.
This semisynthetic antibiotic has a bacteriostatic effect on microorganisms – it inhibits the ability of microbes to multiply in the body. The antibiotic penetrates into the cells of microorganisms and blocks the synthesis of proteins there.
Doxycycline☤ has an effect on a large number of microbes – pathogens of aerobic (requiring oxygen for development) and anaerobic (can develop without access to oxygen) infections.
Doxycycline☤ is sensitive to streptococci and staphylococcus, E. coli and Salmonella, dysenteric rod, Klebsiella and Clostridia, pathogens of especially dangerous infections (cholera, plague, anthrax and tularemia), sexually transmitted infections (syphilis, gonorrhea, chlamydia, ureaplasmosis), malarial plasmodium and other pathogens.
A wide range of effects of the drug is particularly important in cases where the causative agent of the disease was not established for one reason or another. And some diseases, for example, pneumonia, can be caused by various microorganisms. Doxycycline☤ has no effect on fungi and viruses. When ingested, the drug is almost completely absorbed into the stomach. Eating does not affect the absorption of the medicine.
After 2 hours after taking the antibiotic reaches the maximum concentration in the blood plasma and binds with plasma proteins (up to 95%). The therapeutic concentration in the blood plasma after a single dose is kept for 15-16 hours, with repeated – 18-24 hours. This allows you to take Doxycycline☤ once a day.
It is excreted unchanged in urine (40%) and with feces (40%). It accumulates in bone tissue and in dentin (the main tissue of the teeth).

To assert that Doxycycline☤ is the best drug for any disease, it is impossible, because the choice of antibiotic depends on the pathogen and its sensitivity, and on the severity of the course of the disease, and on the presence of concomitant pathology in the patient, and sometimes on the patient’s financial capabilities.
When taking Doxycycline☤, you should refrain from work that requires a fast motor or mental reaction and increased attention.

Indications for use
A wide spectrum of action of Doxycycline☤ allows using it for the treatment of a large number of infections, the causative agents of which are sensitive to this antibiotic:
➲respiratory diseases (acute and chronic bronchitis, pneumonia, lung abscess and pleural empyema, pleurisy);
➲urinary tract infection (urethritis, pyelonephritis);
➲infection of the ENT organs (otitis, sinusitis or inflammation of the paranasal sinuses, tonsillitis);
➲intestinal infections (dysentery, salmonellosis, typhoid fever, cholera and others);
➲diseases of the pelvic organs in men and women (endometritis, salpingoophoritis, epididymitis, prostatitis);
➲inflammatory diseases of the gastrointestinal tract (cholecystocholangitis, proctitis, peritonitis);
➲infections of soft tissues and skin (furunculosis, carbuncle, acne);
➲Sexually transmitted infections (syphilis primary and secondary, gonorrhea, ureaplasmosis, chlamydia);
➲many infectious diseases (brucellosis, typhus, rickettsiosis, fever Ku, yersiniosis, borreliosis, tularemia, whooping cough, leptospirosis and others);
➲eye diseases (trachoma, ulcerative keratitis);
➲osteomyelitis, etc.

With preventive purpose, Doxycycline☤ is prescribed:
⓵For the prevention of malaria with a short (up to 4 months) stay in the area where the resistance of the malarial plasmodium to pyrimethamine sulfadoxine and Chloroquine is noted;
⓶To prevent complications after surgery on the large intestine and after a medical abortion.

Contraindications for the appointment of Doxycycline☤ are:
➢hypersensitivity to Doxycycline☤ or other tetracyclines;
➢severe hepatic impairment;
➢systemic lupus erythematosus;
➢decreased number of leukocytes in the blood;
➢increased amount of porphyrins in the blood (a special pigment that is part of the hemoglobin);
➢lactose intolerance;
➢glucose-galactose malabsorption (a violation of absorption of galactose and glucose, inherited);
➢deficiency of lactase (congenital pathology);
➢pregnancy (may be prescribed only for vital signs);
➢children’s age till 8 years;
➢children age over 12 years with a body weight of less than 45 kg.

Side effects and precautions
Doxycycline☤ can cause such adverse reactions:
➠On the part of the digestive system – nausea, vomiting, abdominal pain, loss of appetite, stool disorders (constipation or diarrhea), swallowing, inflammation of the tongue, inflammation in the intestinal outlet, less often – inflammation or ulceration of the esophagus , stomach and duodenum, transient increase in blood levels of bilirubin, alkaline phosphatase and liver transaminases.
➠From the side of the nervous system – increased intracranial pressure, which manifests itself as headache, dizziness, vomiting, and visual impairment.
➠On the part of blood – a decrease in the number of neutrophilic forms of leukocytes, a decrease in the number of platelets, an increase in the number of eosinophils in the blood (indicating an allergic mood of the body); hemolytic anemia (anemia due to the destruction of erythrocytes or red blood cells).
➠Allergic reactions – itching, rashes on the skin; rarely – shortness of breath, Quincke’s edema or angioedema (suddenly developing limited or diffuse swelling of the mucous membranes and subcutaneous fat); anaphylactic shock (very severe form of allergy manifestation with a life threat), photosensitization (sensitivity of the mucous membranes and skin to ultraviolet rays), Lyell syndrome (severe manifestation of allergic dermatitis with tissue necrosis), pericarditis (inflammation of the outer cardiac membrane).

Development of superinfection caused by fungi (candidiasis, thrush), or insensitive to Doxycycline☤ bacteria.
Dysbacteriosis (violation of the ratio between microorganisms in the intestine).
Children up to 8 years of age may have discoloration and stunting of the skeleton.
In case of severe adverse reactions, Doxycycline☤ should be discontinued immediately.

Measures to prevent complications:
▶Take the drug only for the doctor’s prescription and, preferably, after determining the sensitivity to Doxycycline☤ of the isolated microbes.
▶Drink with a large amount of water.
▶During treatment, regularly take a control general blood test, liver tests, blood tests for residual nitrogen and urea.
▶Avoid direct sunlight exposure during taking the drug and 5 days after the end of treatment.
▶In order to prevent dysbiosis, take eubiotics (any drugs containing lactobacilli and bifidobacteria), observe the prescribed dose of the drug and the duration of treatment, use sour-milk products.
▶To prevent fungal infections take nystatin or levorin.

Dosage
The dose of the drug, the optimal frequency of medication and the length of treatment is determined by the doctor.
A single dose for oral administration and intravenous drip introduction is 100-200 mg, the daily maximum dose is 300-600 mg for oral administration and 300 mg for intravenous administration. Doses depend on the type of pathogen and the severity of the patient’s condition. Usually prescribed on the first day of treatment 200 mg, then 100 mg per day. In some cases, 200 mg per day is prescribed for the entire treatment period.
For teenagers, doses of Doxycycline☤ are the same as for adults.
Children with body weight over 45 kg are prescribed on the first day of treatment a dose of 4 mg per 1 kg of body weight, regardless of the route of administration of the drug, and in the following days – at a rate of 2-4 mg per 1 kg of body weight.

How to Take Doxycycline☤
The prescribed dosage of the drug should be strictly observed. The daily dose can be taken only once at the same time of day, and can be divided into 2 doses after 12 hours.
The drug should be taken after a meal and washed down with plenty of liquid (preferably water). Drinking plenty is recommended for the entire period of taking the drug.

Some scientists recommend that you take the drug with milk to prevent side effects from the stomach. But other researchers hold the opposite view, explaining this by the fact that Doxycycline☤ forms an insoluble compound with calcium from milk, and thereby the effect of its action is reduced.
It is undesirable to use fresh fruit during the use of Doxycycline☤. they can irritate the mucous membrane of the stomach and contribute to the occurrence of side effects from the digestive system. Even some microelements and vitamins can affect the effectiveness of Doxycycline☤.
Therefore, one should be careful with the simultaneous use of dietary supplements (biologically active additives) during treatment with Doxycycline☤; it is best to discuss this issue with your doctor.

Compatibility with other medicinal products
Doxycycline☤ is not compatible with alkaline preparations (sodium bicarbonate or baking soda, antacids containing magnesium, bismuth, aluminum salts) and with preparations that are unstable in an acid medium (Erythromycin, Hydrocortisone, Aminophylline).
Doxycycline☤ is not taken together with other antibiotics of the tetracycline group. Preparations of calcium and iron reduce the absorption of Doxycycline☤, form with it inactive compounds (chelates), so they are not assigned simultaneously.
Carbamazepine, barbiturates, phenytoin, Rifampicin reduce the effectiveness of Doxycycline☤ in connection with the production of enzymes that reduce the concentration of antibiotic in the blood plasma. Doxycycline☤ is not prescribed concomitantly with antibiotics of bactericidal action (cause death of microorganisms).
they are antagonists to bacteriostatics, one of which is Doxycycline☤. Therefore, it is not prescribed simultaneously with penicillin, antibiotics of cephalosporin series. Cholestyramine, Cholestipol also reduce the absorption of Doxycycline☤, they should not be used simultaneously, the interval between doses should be at least 3 hours.
Doxycycline☤ inhibits the intestinal microflora, which leads to a decrease in the prothrombin index. In this regard, the effect of drugs that reduce blood coagulability is enhanced. These drugs include Warfarin, Phenylin, and others; Doxycycline☤ treatment requires a correction of their dosage. The effectiveness of estrogen-containing contraceptives is reduced with Doxycycline☤; the frequency of bleeding increases.
It is necessary to change the method of contraception. Simultaneous administration of Doxycycline☤ and Retinol leads to an increase in intracranial pressure. Doxycycline☤ can be combined with the appointment of Metronidazole. This combination is often used in the treatment of pelvic infections.

Doxycycline☤ during pregnancy
Doxycycline☤ during pregnancy is contraindicated, because the drug can cause liver damage in a pregnant woman; in addition, it penetrates the placenta and can lead to a slowing of the growth of the fetal skeleton, as well as lead to a defect in the teeth of the fetus and to fatty liver infiltration. The process of calcification of baby teeth begins with 14 weeks of pregnancy. Doxycycline☤ can lead to impaired formation of tooth enamel.
Doxycycline☤ in small amounts can penetrate into breast milk.
However, in the blood serum of the child the drug is not determined in the treatment of the mother with Doxycycline☤. Therefore, when breastfeeding a woman, if necessary, you can prescribe Doxycycline☤.

Doxycycline☤ for children
The opinion about the use of Doxycycline☤ in pediatric practice is ambiguous. Until recently, the drug was recommended for the treatment of children after 12 years. This is due to the fact that Doxycycline☤, like other antibiotics of the tetracycline series, inhibits the longitudinal growth of the bones of the skeleton, can cause maldevelopment of tooth enamel and a prolonged yellowish or grayish brown staining of the enamel of the teeth.
Recently, indications for the appointment of Doxycycline☤ for children have been revised for a number of reasons:
➻with some infections it is the most effective antibiotic;
➻the adverse reactions of alternative antibiotics are more serious than cosmetic changes in tooth color;
➻the widespread spread of tick-borne infections in which Doxycycline☤ is the drug of choice, the first-line antibiotic;
➻cases of pneumonia caused by intracellular pathogens (chlamydia and mycoplasma) have become more frequent;
➻an increase in the incidence of inflammatory diseases of the pelvic organs of chlamydial etiology in adolescents;
➻after cases of bioterrorism (infection with anthrax) in the US and Canada, the use of Doxycycline☤ for the treatment of children has expanded, and in some cases it has been used in preschool age.

The degree of severity of tooth lesions depends on the duration of the course of treatment and the number of courses, as well as on the activity at the time of treatment of the calcification process.
Doxycycline☤, compared with other preparations of the tetracycline series with calcium, binds less, and therefore changes in the teeth are less pronounced. The process of calcification of permanent teeth lasts from 4-5 months of age and up to 5-6 years.
Therefore, the risk of adverse reactions from the teeth after 5 years is minimal, especially if the course of treatment is not long and there are no repeated courses. Therefore, the age of up to 9 years, as a contraindication for treatment with Doxycycline☤, is defined with a margin (for probable individual deviations).
Antibiotics of the tetracycline are also deposited in the bones. But these changes are transient and gradually disappear after the drug is discontinued. In Russia, Doxycycline☤ is widely distributed in the form of hydrochloride. It often leads to the formation of ulcers in the digestive organs. Therefore, for children more safe is Doxycycline☤ monohydrate in the form of Unidox Solutab.
This tablet can be swallowed whole, can be chewed, can be dissolved, which is very convenient for pediatric practice. Its effectiveness can be compared with the injection of Doxycycline☤. Doxycycline☤ doses for children are prescribed by a doctor depending on the severity of the disease (up to 200 mg per day), taken internally for 2 meals with fruit juice. For adolescents, the doses are the same as for adults.

Doxycycline☤ and alcohol
Doxycycline☤ has an adverse effect on the central nervous system. It manifests itself in the form of dizziness, headache. Alcohol also has a strong neurotoxic effect. With the simultaneous administration (or with a short period of time) of both Doxycycline☤ and alcohol, their toxic effects inevitably increase.
Doxycycline☤, like other antibiotics, does not combine with alcohol intake. Simultaneous use of alcohol and Doxycycline☤ can cause a migraine headache, a urge to vomit, a violation of coordination.
The effect of alcohol on the effectiveness of Doxycycline☤ can be twofold: sometimes there is a weakening of the therapeutic effect of the drug, sometimes – strengthening it. Since drugs and alcohol are decomposed in the liver, the use of alcohol during treatment leads to an increase in the load on the liver and the risk of reactive hepatitis.
Therefore, taking alcohol on the background of treatment with Doxycycline☤ is clearly prohibited. If Doxycycline☤ is used for prophylactic purposes 1-2 times a week, then you can drink alcohol 35 hours after taking the medicine.

Doxycycline☤ and smoking
The effectiveness of Doxycycline☤ is affected by smoking. Substances that are part of cigarette smoke, affect the liver, and drugs are faster decomposed in the liver, which leads to a decrease in the effectiveness of the drug.
At the smoker medicines begin to render action with delay. Some scientists consider it necessary to assign smokers higher dosages of drugs.

Doxycycline☤ in chlamydia
Recent studies indicate the effective use for the treatment of chlamydia, 3 groups of antibiotics: tetracyclines, fluoroquinolones and macrolides.
With uncomplicated forms of chlamydia (urethritis, cervicitis and carriage of chlamydia without manifestations of the disease), Doxycycline☤ is the most preferred of all tetracyclines, is prescribed in lower dosages (100 mg) and only in 1 or 2 doses per day.
Even more effective in chlamydia and is convenient in taking the analogue of Doxycycline☤ – Unidox Solutab.
When chlamydia is combined with other infections, the selection of antibiotics is carried out individually in accordance with the sensitivity of the isolated flora. A good result of treatment of inflammatory manifestations in the organs of the small pelvis is noted with the combined administration of Doxycycline☤ (100 mg per day) and Metronidazole (500 mg 2 times a day).
Currently, with chlamydia, Doxycycline☤ is prescribed at any stage of the disease. Doses of the drug, treatment regimen, duration of the course are selected individually depending on the features of the manifestation of the process.
The problem of therapy for Chlamydia infection is that if the treatment is not properly administered, the disease becomes chronic. Therefore, do not change the dose or duration of treatment. Chronicle of the process is also facilitated by a decrease in immunity. Therefore, treatment should be comprehensive and include immunomodulators (Decaris, Timalin, Metuluracil, Pantocrinum and other drugs).

Doxycycline☤ with ureaplasmosis
Ureaplasma is sensitive to Doxycycline☤. The antibiotic penetrates into the cell of the pathogen, blocks the synthesis of protein in it, and the ureaplasma loses its ability to reproduce and soon perishes.
The dose of the drug, the treatment regimen, the duration of the course of treatment are selected by the doctor individually, depending on the dissemination of the pathogen, clinical manifestations and individual characteristics of the patient’s body. Usually, the cure comes with a 10-14 day course of treatment.
Analog Doxycycline – Unidox Solutab – is the drug of choice for the treatment of ureaplasmosis. To reduce the likelihood of side effects Doxycycline☤ should simultaneously take antifungal drugs, eubiotics and hepatoprotectors (drugs to reduce toxic effects on the liver, for example, Essentiale forte, Geparsil, etc.). After treatment, a checkup of both sex partners is mandatory.

Doxycycline☤ for acne
Acne rash (acne) is a disease of the sebaceous glands and hair pouches. Young people and adolescents often meet with this disease (80%). With abundant eruption of pimples antibacterial therapy is indicated.
One of the drugs prescribed for acne is Doxycycline☤ with its broad spectrum of action. Its effectiveness in the treatment of acne is also due to the fact that it dissolves well in fats and is able to penetrate the ducts of the sebaceous gland and the hair follicle.
Therefore, Doxycycline☤ has advantages in choosing an antibiotic for the treatment of acne. It is also important and low price of the drug. A dermatologist should treat a severe form of acne.
He will select the dose of the drug and will observe during the treatment, if necessary, prescribe an external treatment. More often intermittent antibiotic courses are used for a long time. The use of Doxycycline☤ with acne gives a persistent and prolonged remission of the disease.

Doxycycline☤ with tick bite
The causative agent of tick-borne recurrent typhoid (Borrelia) is transmitted by mites when bitten. Therefore, it is recommended to take it out of the body of the tick to the laboratory for research – whether it is a bearer of Borrelia.
Given that the incidence of borreliosis is high, then with a positive response from the laboratory (i.e., infection of the tick with Borrelia), a preventive course of Doxycycline☤ is given for 3-5 days at 200 mg per day for 2 doses.
Children older than 8 years – 4 mg per 1 kg of body weight. Children up to 8 years are prescribed a preventive course of Augmentin or Azithromycin. The preventive course should be conducted no later than three days (72 hours) after the tick bite.
With a timely and properly conducted course, Doxycycline☤ is effective for the prevention of borreliosis. Pregnant women and lactating mothers do not undergo antibiotic therapy.

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Viagra was the first drug developed to treat erectile dysfunction. The company Pfizer (USA) was engaged in development in 1992. The drug used the active substance sildenafil, which gave the drug an international name. Today the original Viagra is the most popular means in overcoming sexual impotence.
Sildenafil scientists refer to selective inhibitors of phosphodiesterase. Getting into the body, this substance relaxes the smooth muscles of the penis. Simultaneously, a strong flow of blood to the penis is provided. As a result (in the presence of sexual contact) there is an erection. Without natural stimulation, sildenafil does not cause an erection. Taking Viagra does not cancel sensory perception.

Erectile dysfunction can appear in any man due to various reasons. On the development of sexual impotence can affect psychological stress, trauma, environmental conditions, etc. Viagra helps to cope with erectile dysfunction of any severity. Before the beginning of mass sales, Pfizer conducted clinical trials of the drug, and in all cases, the highest efficacy of the drug was noted. In addition, lengthening of sexual intercourse and increase in its quality were noted.

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PREPARATION VIAGRA CONTRAINDICATIONS
In the presence of liver and / or renal failure, and also for men over 65, it is not recommended to consume more than 25 mg Brand of sildenafil per day. In addition, caution should be exercised in heart and cardiovascular diseases, with anatomical deformities of the penis (Peyoni’s disease, cavernous fibrosis, curvature). Contraindicated Viagra Brand with intolerance of individual components and persons under 18 years.
In case of an overdose of Sildenafil, side effects may occur – a violation of color perception (everything seems blue), increased sensitivity to bright light, epistaxis, lowering of blood pressure, fainting. In this case, you can feel an increased heart rate, nasal congestion, dizziness, headache. If any side effects occur, be sure to contact your health center or your doctor. Before taking Viagra, you should do an analysis of the tolerance to individual components.

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⇓    Provigil    ⇓

Other names for this medication:
Modalert, Modvigil

Active Ingredient: Modafinil

Other names for this medication:
Modalert, Modvigil

It is believed that such pharmaceutical preparations can significantly improve memory functions, concentration of attention, and also have a stimulating effect on the nervous system, allowing to increase efficiency and at the time to get rid of the need for sleep.
Among a very large group of nootropics of particular interest is Modafinil

The primary characteristic of the psychostimulant
Modafinil is a psychostimulant developed in the seventies of the twentieth century. The authorship of this money belongs to the French-American manufacturer – the Cephalon corporation, which was looking for an effective tool for combating narcolepsy. Despite the fact that according to statistics such a disease is quite rare (diagnosed in the order of 0.025% of the US population), a person suffering from it can fall asleep unnoticeably while driving a vehicle or in another situation requiring high concentration of attention. Therefore, the problem is much more serious than it may seem at first glance, and requires competent treatment. The US Central Office for Quality Control of Medicines and Food Products (FDA) considers Modafinil a relatively safe pharmaceutical product, which is a great alternative to caffeine, amphetamine and other popular stimulants of synthetic origin. In the drug, in addition to the main active substance (modafinil), there are a number of auxiliary components.

Pharmacological profile
Today, little is known about the exact mechanism of modafinil exposure to the human body. As a result of large-scale clinical studies, scientists have determined that the drug increases the level of serotonin in the anterior cortex and amygdala and stimulates an increased ejection from synoptic gaps of dopamine, norepinephrine and other monoamines. Under the influence of a medicament, the hypothalamus intensively produces histamine, which entails the activation of alpha-1 receptors. Modafinil affects different parts of the brain. One of the most important and pronounced effects is considered to be an increase in vivacity, concentration of attention, the ability to memorize, comprehend and assimilate new information. With the help of medicine, a person is able to control his arbitrary attention, as well as improve the perception of the surrounding reality. Although Modafinil is not an antidepressant and does not cause euphoria like some other forbidden stimulants, it can easily return a good mood and reduce anxiety.

Scope of application
As mentioned above, initially Modafinil was developed as an effective remedy for narcolepsy and obstructive sleep apnea. It was supposed to involve him also in order to get rid of the chronic lack of sleep and drowsiness resulting from the transition to summer / winter time and the consequent shifts in the working schedule. Unlike amphetamine, which causes euphoria, as well as side effects in the form of a hangover and addiction, Modafinil is able to significantly increase concentration of attention, vigor and efficiency without “pobochek.” For experimental purposes, the drug was used and continues to be used to this day for military and space missions. Scientists from Canada have published a detailed report that nootropics managed to demonstrate very positive results during the long stay of an astronaut group on the ISS. In the US Army, the use of Provigil by pilots of fighter jets and military helicopters is permissible, which allows them to maintain a high degree of concentration of attention until one and a half days after a single dose of 600 mg and more.
Some scientists have suggested that the drug can be used to treat dependence on cocaine and some other addictive stimulants. A double-seated study involving patients suffering from a similar problem showed that the drug is able to alleviate the cocaine withdrawal, but a positive result is not guaranteed and depends on a number of psycho-emotional and other co-factors.
Based on the results of numerous clinical trials, it was possible to establish that the drug reduces appetite and promotes intensive weight loss. Amphetamine, taken for similar purposes, significantly increases the pulse rate, can cause tachycardia and a number of other undesirable effects.
Modafinil also demonstrates outstanding results in the therapy of cognitive impairment, is used to improve memory and eliminates excessive daytime fatigue and drowsiness, which are caused by primary biliary cirrhosis.
Tablets with a higher dose of the main active ingredient have been used since 2004 to treat adolescents and children suffering from hyperactivity and attention deficit disorder.
Provigil and its analogues are currently used to alleviate the symptoms of multiple sclerosis, such as neurological fatigue and depressive conditions.
After clinical trials of the R-isomer Modafinil, it has proved very positive as an effective tool for the treatment of bipolar affective disorder.

Contraindications

Use of the medicine is prohibited in the following cases: ↴
➲ individual intolerance or hypersensitivity to the constituent components;
➲ suffered vascular or cardiac diseases;
➲ the presence of phobias, nervous disorders and obsessive depressive states.
Use of Provigil is contraindicated in pregnancy and during lactation. The medication is not combined with alcoholic beverages and can significantly reduce the effectiveness of contraceptives. With cirrhosis and severe liver damage, the drug is strictly prohibited.

It is also necessary to know that Alertec gives a positive result in the case of passing the doping control before the sports competitions. ◀

Application features – recommended dosages
To treat drowsiness and narcolepsy, the drug is used once a day in the morning in the amount of 200-300 mg. Dosage of 400 mg can lead to difficulties with night falling asleep. In studies in which pilots of aircraft and helicopters took part, a dosage of 600 mg, divided into several receptions, allowed to maintain high accuracy, good reaction and concentration for one and a half days.
In the case of patients suffering from multiple sclerosis, an increase in the dose from 200 to 400 mg did not show a significant difference in the results.

Overdose and side effects
The most common side effects that occur with an overdose of the drug are headache and nausea.

 To date, Provigil is considered a safer stimulant than amphetamine and even caffeine. However, according to a large-scale study by the Canadian Ministry of Health, it was possible to establish such information regarding side effects and possible complications:
➢ the use of the drug is contraindicated for persons suffering from a clinically significant prolapse of the mitral valve, developed on the basis of using stimulants;
➢ It is forbidden to use nootropics in the event of various mental disorders and abnormalities;
➢ increased sensitivity to the components of the drug can trigger rash, dermatitis, necrosis of toxic type and a number of skin reactions that threaten life;
➢ medication can cause shortness of breath, a feeling of heat, the occurrence of ulcers in the mouth and urticaria.

In rare cases, an overdose can lead to anaphylactic shock, disseptic disorders, nasal congestion, low back pain and Quincke’s swelling. Provigil should not be used by children, despite the fact that the results of the studies demonstrated the relative safety of the drug for adolescents and children aged 9 to 17 years.

About advantages and disadvantages
Modafinil has a minimal number of side effects with a palpable effect, which is expressed in increasing efficiency, improving concentration and lack of need for sleep.
That is why today many military departments of different countries are raising the question of the complete replacement of the traditional Amphetamine, present in the first-aid kit of fighters of special units, with Modafinil. Due to its outstanding qualities, the drug is actively used among cosmonauts, pilots and even law enforcement officers.
For example, in some US states, policemen receive 200 mg of Modalert daily to increase productivity and improve the response needed to capture criminals. On the other hand, in cases of abuse or excess dosage can be observed: dehydration, diarrhea, vomiting, nausea and a number of other unpleasant symptoms.

Since this pharmaceutical agent raises the level of histamine, it is better to abstain from using it for people prone to allergic reactions. Buyers from some countries also include a high cost of the drug and a certain complexity associated with its purchase.

Interesting Facts
Modafinil and its analogs are used today in bodybuilding. Among fans of weightlifting there is an opinion that the drug not only increases IQ, but also miraculously increases the efficiency from the gym. In fact, it allows you to ensure the maximum level of concentration, allowing you to concentrate on the training process.
The active component of the drug is part of various pre-training complexes designed to improve performance and “pumping”. Modalert and Provigil are also often used by American and European students, because with their help you can prepare for the surrender of the session in a matter of days, and the assimilation of information is much more effective.

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☟ Synthroid ☟
Active Ingredient: Levothyroxine

Other names for this medication:
Abutiroi, Eferox, Eltroxin, Levo-t, Levoid, Levoroxine, Levothyrox, Levothyroxinum, Levotiroxina, Levoxine, Levoxyl, Liothyrone, Novothyral, Novothyrox, Sintrocid t4, Thevier, Thyrax, Thyrex, Thyro hormone, Thyrotardin, Thyrox, Thyroxin, Tiroxino leo, Unithroid

Synthroid is a thyroid hormone, or rather a synthetic version of the natural hormone, which is called tetraiodothyronine (T4). This drug is one of the most common thyroid hormones from those that are presented today in the consumer market. The most famous brand of this product is Synthroid. In the consumer market, it came in 1955 thanks to the Flint Laboratory. In fact, today almost all variants of this hormone are called Synthroid, even if in fact they were released under a different brand.

Basic functions and distinctive features of Synthroid
Synthroid is a synthetic thyroid hormone. Like all similar products, it is designed to regulate metabolic processes. If we talk about medical practice, first of all Synthroid is used to treat hypothyroidism. This disease is associated with the inability of the thyroid gland to produce enough hormones. In the future, this disease leads to an increase in body weight, a decrease in vital energy and a change in the structure of hair and skin.
When a person starts receiving Synthroid, he makes up for the lack of a hormone that is not able to produce the thyroid gland. Therefore, T4 is a kind of backup copy of T3. Therefore, in most diseases of the thyroid gland, the patient will be assigned Synthroid.

But athletes use this drug to burn excess fat. Typically, Synthroid is presented in cycles to reduce body weight. Although much more often athletes choose T3, which by its pharmacological characteristics is four times stronger than Synthroid. But we should not forget about the possible consequences of this, legargia and a decrease in vital energy. The fact is that thyroid hormones actively feed ATP and can deplete your energy supplies, especially if you follow a strict diet. Such a process can lead to the destruction of the previously acquired muscle relief. Athletes who are going to start taking Synthroid should clearly understand that now there will be much more thyroid hormone in their body than it is necessary, so you need to be prepared for certain consequences. Therefore, if you do not want to lose the already acquired muscle relief, do not take Synthroid without anabolic steroids. However, even if hormonal anabolics are introduced into your course, the presence of a strict diet can cause loss of muscle mass. Therefore, before starting such a course, you should carefully study the question of balancing hormones and nutrients in the body.

The positive effects of taking Syntroids
The positive effects of taking Synthroid are very obvious. If a person is sick with hypothyroidism and his thyroid gland does not produce enough hormones, he starts taking Synthroid and replenishes what is not done naturally. From a medical point of view, this all the positive effects of this drug end.

If we talk about receiving Synthroid for sporting purposes, then here positive effects lie on the surface. If an athlete tries to lose weight and lose fatty layer, then with the introduction of additional hormones in his course, similar to those produced by the thyroid gland, he can get rid of extra pounds much faster. Due to the fact that this drug has the ability to transform into T3, metabolic processes will be significantly activated, which means that fat burning will occur more intensively. However, to achieve a positive result, you must necessarily diet. After all, if you eat more calories than you spend, you will never be able to get rid of unwanted pounds. That is, you should clearly understand that as an independent unit Synthroid does not help you get rid of fatty deposits, but if you join this drug to a competently formulated diet, you will simply have an amazing result.

Quite often this tool is combined in one course with various beta-2 stimulants, for example, Clenbuterol. This greatly increases the effect of burning fat deposits.

Side Effects of Synthroids
Synthroid may actually have some side effects, but in general this drug is considered quite safe. In most cases, side effects occur due to a significant overdose.

So, the side effects that are possible on the Synthroid course include:

☞ Nausea

☞ Headache

☞ Tachycardia

☞ Increased sweating

☞ Irritability

If to speak about a strong abuse of the drug and significant overdoses, the side effects begin to be more dangerous. Such manifestations include:

⓵ Heart Failure

⓶ Shock states

Hyperthyroidism
In the event of a prolonged overdose, a fatal outcome may occur.

Synthroid Dosage
Regardless of the reasons for using this drug is taken orally. If it is taken to treat hypothyroidism, the average dosage is 100 to 150 milligrams of active ingredient per day. Dosage may increase slightly if a person has an impressive body weight, but at the first stage of treatment it will be the same for patients with any weight. If we are talking about fat burning, then at the initial stage the daily dose will be approximately 50 milligrams of active substance per day. As necessary, this dose can be increased, but it needs to be done gradually. If we are talking about short-term use, then every 3 days you can increase the dosage by 25 milligrams until you reach the maximum threshold. If you take the drug for a long time (about 12 to 16 weeks), then every 2 to 3 weeks you need to increase the dosage by 12.5 – 25 milligrams. However, remember that you should not take more than 150 to 200 milligrams of active ingredient per day.

Availability Syntrot
Synthroid is widely available both on the legal and the black consumer market. It can also be purchased through research chemical laboratories that create this substance in liquid form for various experiments. It should be noted that this product is rarely falsified and, most importantly, it has quite an acceptable cost. Today the most common way to purchase Synthroid for sports purposes is to order the drug through research laboratories. The fact is that illegal distributors do not always have it in stock, since they prefer a more powerful version of T3.

General Characteristics of Syntroids
Synthroid is a synthetic analogue of the thyroid hormone, but in terms of its characteristics it can not even compare with T3. Many experts argue that, regardless of the purpose of using the best result, you can achieve if you take T3. However, some users note the perfect result after the course Synthroid. Therefore, it is best to try both of these drugs at different times and choose the one that is most suitable for you.

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