Oxymethlone IH 50mg by Iran Hormone

Androlic / Anadrol (Oxymethylone)
Androlic / Anadrol tablets. Each anadrol tablet contains 50 mg. oxymetholone. Androlic / Anadrol, brand name Androlic, comes in packs of 20 tablets and is manufactured by The British Dispensary (L.P.) Co. Ltd. .

Common uses and directions for anadrol
The primary medical uses of anabolic-androgenic steroids are to treat delayed puberty, some types of impotence and wasting of the body caused by HIV infection or other diseases.

Anabolic steroids promote the growth of skeletal muscle and the development of male sexual characteristics but do also have some other effects.

Androlic / Anadrol 50 is the strongest and, at the same time, also the most effective oral steroid. Androlic / Anadrol has an extremely high androgenic effect, which goes hand in hand with an extremely intense anabolic component - oxymetholone.

The highly androgenic effect of anadrol stimulates the regeneration of the body so that the often feared "over training" is unlikely to occur.

A dosage sufficient for any athlete would be 0.5 - 0.8 mg. per pound of body weight/day. This corresponds to 1-4 tablets; i.e. 50-200 mg/day. Under no circumstances should an athlete take more than four tablets in any given day, preferrably never more than three.

When taking anadrol for the first time the athelete should begin with an intake of only one 50 mg tablet. After one week the daily dosage can be increased to two tablets, one tablet each in the morning and evening, taken with meals.

Higher dosages should not be taken for periods longer than two to three weeks. Any use of anadrol should not exceed six weeks. After discontinuing anadrol, it is important to continue steroid treatment with another compound since, otherwise, a drastic reduction of muscle mass and strength takes place.

Androlic / Anadrol is the most harmful oral steroid and its intake can cause many considerable side effects. Most users can expect certain pathological changes in their liver values after approximately one week. Those who discontinue the use of oxymetholone will usually show normal values within two months. Oxymetholone is the only anabolic/androgenic steroid, which is linked with liver cancer.



Androlic / Anadrol (Oxymethylone) additional information:
Common uses
The primary medical uses of anabolic-androgenic steroids are to treat delayed puberty, some types of impotence and wasting of the body caused by HIV infection or other diseases.

Anabolic steroids promote the growth of skeletal muscle and the development of male sexual characteristics but do also have some other effects.

Androlic / Anadrol 50 is the strongest and, at the same time, also the most effective oral steroid. Androlic / Anadrol has an extremely high androgenic effect, which goes hand in hand with an extremely intense anabolic component - oxymetholone.

The highly androgenic effect of anadrol stimulates the regeneration of the body so that the often feared "over training" is unlikely to occur.

Androlic / Anadrol can give dramatic gains in strength and muscle mass in a very short time. Water retention is considerable and since the muscle cell draws a lot of water, the entire muscle system of most athletes will look smooth. Androlic / Anadrol does not cause a qualitative muscle gain but rather a quantitative one. Androlic / Anadrol "lubricates" the joints since water is stored there as well. On the one hand this is a factor in the enormous increase of strength and, on the other hand, it allows athletes with joint problems a painless workout. A strict diet, together with the simultaneous intake of Nolvadex-D and Proviron , can significantly reduce water retention.

Androlic / Anadrol increases the number of red blood cells, allowing the muscle to absorb more oxygen. The muscle thus has a higher endurance and performance level.

Although anadrol is not a steroid used in preparation for a competition, it does help more than any other steroid during dieting to maintain the muscle mass and to allow an intense workout.

Directions
Androlic / Anadrol comes as a tablet containing 50 mg. oxymetholone, to take by mouth.

A dosage sufficient for any athlete would be 50-200 mg/day. depending on weight and how advanced user of anabolic steroids the athlete is. An intake of more than three tablets in any given day is not advisable.

The first time user of anadrol should begin with an intake of only one 50 mg tablet. After a one week, the daily dosage can be increased to two tablets, one tablet each in the morning and evening, taken with meals.

Athletes who are more advanced or weigh more than 220 pounds can increase the dosage to 150 mg/day in the third week. This dosage, however, should not be taken for periods longer than two to three weeks.

The use of anadrol should never exceed six weeks. After discontinuing the use of anadrol, it is important to continue steroid treatment with another compound since, otherwise, a drastic reduction of muscle mass and strength takes place and the user. Athletes continue their treatment with injectable testosterone such as Sustanon 250 or Testosterone Enanthate for several weeks.

Precautions
Androlic / Anadrol is the most harmful oral steroid and its intake can cause many considerable side effects. Most users can expect certain pathological changes in their liver values after approximately one week. An increase in liver values of both the enzymes GOT and GPT also called transaminases, often cannot be avoided, which are indications of hepatitis, i.e. a liver infection. Those who discontinue oxymetholone will usually show normal values within two months.

Longer intake of anadrol and/or higher doses can cause a yellow discoloration of fingernails, eyes, or skin. The liver enzyme gamma-GT also reacts sensitively to the oxymetholone, causing it to elevate. If high dosages of anadrol are taken over a long period, there is an increased risk that the described liver changes could end up damaging the liver. During the intake of Androlic / Anadrol 50, the liver values as well as the LDH/HBDH quotient, should always be checked by a competent physician.

Oxymetholone is the only anabolic/androgenic steroids which has been linked with liver cancer.

Androlic / Anadrol is not recommended for women since it causes many and, in part, irreversible virilizing symptoms such as acne, clitorial hypertrophy, deep voice, increased hair growth on the legs, beard growth, missed periods, increased libido, and hair loss.

Possible side effects
Oxymetholone easily converts into estrogen which causes signs of feminization and the already mentioned water retention, which in turn requires the intake of antiestrogens. The increased water retention, in addition to the aesthetical problems, can be further detrimental since it may cause high blood pressure. In extreme cases the intake of an anti-hypertensive drug may be necessary.

Oxymetholone does not convert to DHT. However, it is a potent androgen. Users who experience severe steroid acne caused by anadrol can get this problem under control by using the prescription drug Accutane.

Other possible side effects may include headaches, nausea, vomiting, stomach aches, lack of appetite, insomnia, and diarrhea. The athlete can expect a feeling of "general indisposition" with the in-take of anadrol which is completely in contrast to Dianabol which conveys a "sense of well-being".

The increased aggressiveness is caused by the resulting high level of androgen and occurs mostly when large quantities of testosterone are injected simultaneously with the use of anadrol.

The body's own production of testosterone is considerably reduced since anadrol has an inhibiting effect on the hypothalamus, which in turn completely reduces or stops the release of GnRH (gonadotropin releasing hormone). For this reason the intake of testosterone-stimulating compounds such as HCG and Clomid is absolutely necessary to maintain the hormone production in the testes.

If you notice other effects not listed above, contact your doctor.

Overdose
If overdose of anadrol is suspected, contact your local poison control center or emergency room immediately.

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Lovegra100mg by Generic

Kamagra is een erectie middel en is vaak beter bekend als een party genots middel. Echter, de werking van Kamagra is identiek aan die van de bekendere merken. Het verschil zit hem puur in de prijs van het produkt, andere producten zijn duurder. 

Verpakt per strip van 4 tabletten.

Wat is Kamagra?

Kamagra 100mg is een erectiepil die in India wordt geproduceerd door Ajanta Pharma, een farmaceutisch bedrijf gevestigd in India. Kamagra 100mg is een generic, dat wil zeggen dat het de zelfde werkzame stof bevat als het bekende gepatenteerde Viagra alleen onder een a ndere naam verkocht wordt. De stof die wordt gebruikt in Kamagra is Sildenafil. Deze stof zit zowel in Viagra als in Kamagra 100mg. Vanwege de werkzame stof in Kamagra 100mg is de werking exact gelijk aan die van Viagra. Kamagra 100mg zorgt voor een constante grote en harde erectie die je ruim 4 tot 5 uur onafgebroken kunt vasthouden bij seksuele opwinding. Wanneer de seksuele stemming heftig genoeg is kunt u zelfs na een orgasme direct weer tot de daad overgaan.

Hoe werkt Kamagra?

In Kamagra 100mg zit de stof sildenafil citraat deze zorgt ervoor dat de aders naar de penis ontspannen en uitzetten en zorgt zo voor een verhoogde bloedstroom naar de penis. Uw zult merken dat uw erectie harder is dan normaal, omdat het bloed tot in de kleinste bloedvaten wordt opgenomen. Wanneer de penis zijn volledige erectie heeft bereikt zorgt sildenafil citraat, de stof die in Kamagra zit verwerkt, ervoor dat de penis het bloed vasthoudt. Kamagra maakt op deze manier een erectie een stuk eenvoudiger.

Ook bij mannen die zonder probleem een erectie kunnen krijgen geeft Kamagra een veel hardere, stevigere en langer durende erectie en zorgt voor veel meer voldoening bij de seksuele activiteiten. Alleen bij ons 100 procent zekerheid van de originele Kamagra 100mg. Bestel vandaag nog en ontdek de werking van Kamagra! Kamagra is een erectie middel, de werkzame stof is Sildenafil Citraat. Dit zelfde citraat zit ook in andere bekende merken. Kamagra is een goedkopere variant en is vaak beter bekend als een party genots middel. Echter, de werking van Kamagra is identiek aan die van de bekendere merken. Het verschil zit hem puur in de prijs van het produkt, andere producten zijn duurder. Op dit moment zijn er veel namaak Kamagra producten op de markt, hiervoor dient u uit te kijken. Kamagra wordt geproduceerd door Ajanta Pharma uit India en is een serieus professioneel bedrijf.

•Kamagra 100 mg  bestellen doet u bij www.leaderentoys.com . Besteld u deze erectie pil op werkdagen  dan wordt die de volgende dag geleverd. Deze erectie pil kopen en bestellen bij goedkoopste webshop www.leaderentoys.com

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Nolvadex 10mg by Astra Zeneca x 1 Strip

Nolvadex 10mg by Astra Zeneca x 1 Strip

This drug is a potent nonsteroidal anti-estrogen. It is indicated for use in estrogen dependent tumors, i.e. breast cancer. Steroid users take Nolvadex to prevent the effects of estrogen in the body. This estrogen is most often the result of aromatizing steroids. Nolvadex can aid in preventing edema, gynecomastia, and female pattern fat distribution, all of which might occur when a man's estrogen levels are too high. Also, these effects can occur when androgen levels are too low, making estrogen the predominant hormone. This can occur when endogenous androgens have been suppressed by the prolonged use of exogenous steroids. Nolvadex works by competitively binding to target estrogen sites like those at the breast.

This drug is not toxic nor have any side effects been seen in athletes who used the drug\' as an anti-estrogen. This drug is the most popular anti- estrogen amongst steroid users.

Although it does not turn out to be 100% effective for everyone, it does seem to exhibit some level of effectiveness for the majority. It works so well for some bodybuilders they can take drugs like Anadrol right up to a contest as long as they stack it with Nolvadex. It would seem wise to take this drug in conjunction with any steroid cycle. Most reported a dosage of 10 mg to 20 mg daily got the job done. Availability of Nolvadex has been fair on the black market.

Protection against bitch tits.

Effective Dose: 1 - 2 tabs/day

Nolvadex (Tamoxifen Citrate)

Description:

by Bill Roberts - Nolvadex is very comparable to Clomid , behaves in the same manner in all tissues, and is a mixed estrogen agonist/antagonist of the same type as Clomid. The two molecules are also very similar in structure.

It is not correct that Nolvadex reduces levels of estrogen: rather, it blocks estrogen from estrogen receptors and, in those tissues where it is an antagonist, causes the receptor to do nothing.

The claim that Nolvadex reduces gains should not be taken too seriously. The fact is that any number of bodybuilders have made excellent gains while using Nolvadex. The belief that it reduces gains seems to stem from the fact that the scientific literature reports a slight reduction in IGF-1 (individuals using anabolic steroids were not studied though) from use of Nolvadex. Thus, Dan Duchaine reported that it reduces IGF-1 and therefore reduces gains. However, if this effect exists at all, it must be very minor, due to the excellent gains that many have made, and from the fact that no one has noticed any such thing from Clomid , which has the same activity profile.

However, I would not be surprised if one were to tell a steroid user that Clomid reduced his gains, he would immediately become afraid that Clomid reduced his gains (please note that no one I have ever heard of has noticed this.) Not having been so misled, however, he would not conclude this from his results. But if an authority publishes that such an effect occurs, whether it does or not it can become self-fulfilling by biasing the user.

The fact that Nolvadex will reduce water retention may result in the user agreeing that gains are less, since weight gain is less, thus reinforcing the bias.

Nolvadex / Tamoxifen

Nolvadex tablets. Each Nolvadex tablet contains 20 mg. tamoxifen. Nolvadex comes in packs of 30 tablets and is manufactured by AstraZeneca.

Common uses and directions for Nolvadex

Nolvadex is used to treat breast cancer in women or men. Tamoxifen may also be used to treat other kinds of cancer, as determined by your doctor.

Tamoxifen also may be used to reduce the risk of developing breast cancer in women who have a high risk of developing breast cancer.

Athletes like to use Nolvadex at the end of a steroid cycle since it increases the body's own testosterone production.

The dose of tamoxifen will be different for different patients. Follow your doctor's orders or the directions on the label. Normally the dose will vary between 20-40 mg./day. Athletes seldom use more than 30 mg./day.

There are many possible side effects that are very different depending on how long time Nolvadex is used as well as depending on the s e x of the user.

Nolvadex (Tamoxifen) additional information:

Common uses

Nolvadex (tamoxifen) blocks the effects of the estrogen hormone in the body. Nolvadex is used to treat breast cancer in women or men but tamoxifen may also be used to treat other kinds of cancer, as determined by your doctor.

Tamoxifen also may be used to reduce the risk of developing breast cancer in women who have a high risk of developing breast cancer.

The exact way that tamoxifen works against cancer is not known, but it may be related to the way it blocks the effects of estrogen on the body.

Many athletes like to use Nolvadex at the end of a steroid cycle since it increases the body's own testosterone production and to prevent estrogenic side effects of taking anabolic steroids.

Since most steroids aromatize more or less strongly, i.e. part of the substance is converted into estrogens, male athletes can experience a significant elevation in the normally very low estrogen level while using anabolic steroids. This can lead to feminization symptoms such as gynecomastia, increased fat deposits and higher water retention.

Nolvadex works against this by blocking the estrogen receptors of the effected body tissue, thereby inhibiting a bonding of estrogens and receptor. Nolvadex does not prevent testosterone and its synthetic derivatives from converting into estrogens, though, but only fights with them in a sort of "competition" for the estrogen receptors. After the discontinuance of Nolvadex a "rebound effect" can therefore occur where the suddenly freed estrogen receptors are able to absorb the estrogen present in the blood. For this reason the combined intake of Proviron. is suggested.

Nolvadex is also useful during a diet since it helps in the burning of fat. Although tamoxifen has no direct fatburning effect its antiestrogenic effect contributes to keeping the estrogen level as low as possible. Nolvadex should especially be taken together with the strong androgenic steroids Dianabol and Anadrol , and the various testosterone compounds.

Directions

Nolvadex comes as a tablet, containing 20 mg. tamoxifen, to take by mouth. Nolvadex tablets are usually taken 1-2 times daily, swallowed whole without chewing, with some liquid during meals.

The dose of tamoxifen will be different for different patients. Follow your doctor's orders or the directions on the label. Common doses are;

For breast cancer in women or men: Adults 20 to 40 mg. daily.

For reducing the risk of developing breast cancer in high-risk women: Adults 20 mg. daily, for five years.

The normal daily dosage taken by athletes is 10-30 mg./day To prevent estrogenic side effects normally 10 mg./day is sufficient, a dosage which also keeps low the risk of reducing the effect of simultaneously taken steroids. Often it is sufficient if the athlete begins this preventive intake of Nolvadex three to four weeks after the first intake of anabolic steroids. Athletes who have tendencies toward gynecomastia, strong water retention, and increased fat deposits with steroids such as Dianabol, Testosterone, Anadrol 50, and Deca-Durabolin usually take 20-30 mg./day The combined application of Nolvadex 20-30 mg./day and Proviron 25-50 mg./day in these cases leads to excellent results. The same is true for athletes who are in competition, and for women. Women, however, should do without the intake of Proviron or at least reduce the dose to one 25 mg. tablet per day.

If you miss a dose of tamoxifen, do not take the missed dose at all and do not double the next one. Instead, go back to your regular dosing schedule and check with your doctor.

Precautions

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For tamoxifen, the following should be considered:

Tell your doctor if you have ever had any unusual or allergic reaction to tamoxifen.

Tell your doctor if you are pregnant or if you intend to become pregnant. Tamoxifen should not be used to reduce the risk of breast cancer if you are pregnant of if you intend to become pregnant. Tamoxifen use in women has been shown to cause miscarriages, birth defects, death of the fetus, and vaginal bleeding.

It is best to use some kind of birth control while you are taking tamoxifen and for about 2 months after you stop taking Nolvadex. However, do not use oral contraceptives since they may interfere with tamoxifene. Tell your doctor right away if you think you have become pregnant while taking Nolvadex.

Breast-feeding is generally not recommended while you are taking tamoxifen.

Tell your health care professional if you are taking any other prescription or nonprescription medicine. If you are taking tamoxifen to reduce the risk of breast cancer, it is especially important that your health care professional know if you are taking the following:

Anticoagulant, coumarin-type blood thinners should not be used with tamoxifen when used to reduce the risk of developing breast cancer in women who have a high risk of developing breast cancer. If you need to take blood thinners, your blood clotting times should be monitored by your doctor.

If you take cytotoxic medicines with tamoxifen, you may have an increased risk of blood clots.

The presence of other medical problems may affect the use of tamoxifen. Make sure you tell your doctor if you have any other medical problems, especially:

Blood problems, cataracts or other eye problems, high cholesterol levels in the blood, blood clots (or history of), pulmonary embolism (or history of), stroke, uterine cancer.

For athletes a disadvantage of tamoxifen is that it can weaken the anabolic effect of some steroids. The reason is that Nolvadex reduces the estrogen level. The fact is, however, that certain steroids, especially the various testosterone compounds, can only achieve their full effect if the estrogen level is sufficiently high. Athletes who predominantly use mild steroids such as Primobolan, Winstrol, Oxandrolone, and Deca-Durabolin should carefully consider whether or not they should take Nolvadex since, due to the compound's already moderate anabolic effect, an additional loss of effect could take place, leading to unsatisfying results.

Possible side effects

Tamoxifen may cause unwanted effects that may not occur until months or years after Nolvadex is used. Tamoxifen increases the chance of cancer of the uterus in some women taking it. Tamoxifen may cause blockages to form in a vein, lung, or brain. In addition, tamoxifen has been reported to cause cataracts and other eye problems.

Check with your doctor as soon as possible if any of the following side effects occur:

Anxiety, blistering, peeling, or loosening of skin and mucous membranes, blurred vision, chest pain, confusion, cough, dizziness, fainting, fast heartbeat, lightheadedness, pain or swelling in fingers, hands and legs, shortness of breath or trouble breathing, weakness or sleepiness, yellow eyes or skin.

For females only;

Change in vaginal discharge, chills, fever, hoarseness, lower back or side pain, pain or feeling of pressure in pelvis, pain, redness, or swelling in your arm or leg, painful or difficult urination, rapid shallow breathing, skin rash or itching over the entire body, sweating, vaginal bleeding, wheezing, absent, decrease in amount of urine, feeling of warmth redness of the face, neck, arms and occasionally, upper chest, menstrual changes, nausea, vaginal bleeding, weight changes, white or brownish vaginal discharge.

The use of Nolvadex may also cause other side effects not listed above to occur. If you notice any other effects, check with your doctor.

Overdose

If overdose of tamoxifene is suspected, contact your local poison control center or emergency room immediately.

Additional information:

Keep Nolvadex in a tightly closed container and out of reach of children. Store Nolvadex at room temperature and away from excess heat and moisture (not in the bathroom).

For more information about Nolvadex, please visit Nolvadex.com.

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Kinz 20mg/1ml (Nalbuphine) by Sami

Kinz Nalbuphine is a synthetic agonist-antagonist of the phenanthrene series. It is chemically related to both the widely used opioid , , and the potent opioid analgesic, oxymorphone. Chemically nalbuphine hydrochloride is 17-(cyclobutylmethyl)-4,5α-epoxymorphinan-3,6α,14-triol hydrochloride. Nalbuphine hydrochloride molecular weight is 393.91 and is soluble in H2O (35.5 mg/mL @ 25ºC) and ethanol (0.8%); insoluble in CHCl3 and ether. Nalbuphine hydrochloride has pKa values of 8.71 and 9.96. The molecular formula is C21H27NO4·HCl.

NUBAIN is a sterile solution suitable for subcutaneous, intramuscular, or intravenous injection. NUBAIN is available in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. Both strengths in 10 mL vials contain 0.94% sodium citrate hydrous, 1.26% citric acid anhydrous, and 0.2% of a 9:1 mixture of methylparaben and propylparaben as preservatives; pH is adjusted, if necessary, to 3.5 to 3.7 with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.

NUBAIN is also available in ampuls in a sterile, paraben-free formulation in two concentrations, 10 mg and 20 mg of nalbuphine hydrochloride per mL. One mL of each strength contains 0.94% sodium citrate hydrous, and 1.26% citric acid anhydrous; pH is adjusted, if necessary, to 3.5 to 3.7 with hydrochloric acid. The 10 mg/mL strength contains 0.2% sodium chloride.

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Getryl (Glimepiride) 2mg

Getryl (Glimepiride oral tablet)
Highlights for glimepiride
Glimepiride oral tablet is available as a generic drug and as a brand-name drug. Brand name: Amaryl.
Glimepiride comes as a tablet you take by mouth.
Glimepiride is used to treat type 2 diabetes. It helps control blood sugar when used along with a healthy diet and exercise.
What is glimepiride?
Glimepiride is a prescription drug. It comes as an oral tablet.

Glimepiride is available as the brand-name drug Amaryl and as a generic drug. Generic drugs usually cost less. In some cases, they may not be available in every strength or form as the brand-name version.

This drug may be used as part of a combination therapy. That means you need to take it with other drugs.

Why it's used
Glimepiride is used to reduce high blood sugar levels in people with type 2 diabetes. It’s used in combination with a healthy diet and exercise.

This medication may be used with insulin or other types of diabetes drugs to help control your high blood sugar.

How it works
Glimepiride belongs to a class of drugs called sulfonylureas. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

Glimepiride helps your pancreas to release insulin. Insulin is a chemical that your body makes to move sugar (glucose) from your bloodstream into your cells. Once the sugar enters your cells, they can use it as fuel for your body.

With type 2 diabetes, your body doesn’t make enough insulin, or it can't properly use the insulin that it makes, so the sugar stays in your bloodstream. This causes high blood sugar levels (hyperglycemia).

Glimepiride side effects
Glimepiride oral tablet doesn’t cause drowsiness, but it can cause other side effects.

More common side effects
The more common side effects that can occur with glimepiride include:

low blood sugar (hypoglycemia). Symptoms may include:
trembling or shaking
nervousness or anxiety
irritability
sweating
lightheadedness or dizziness
headache
fast heart rate or palpitations
intense hunger
fatigue or tiredness
headache
nausea
dizziness
weakness
unexplained weight gain
If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects
Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

severe low blood sugar (less than 35 to 40 mg/dL). Symptoms may include:
mood changes, such as irritability, impatience, anger, stubbornness, or sadness
confusion, including delirium
lightheadedness or dizziness
sleepiness
blurred or impaired vision
tingling or numbness in your lips or tongue
headaches
weakness or fatigue
lack of coordination
nightmares or crying out in your sleep
seizures
unconsciousness
hypersensitivity (allergic) reactions. This drug can cause several types of allergic reactions, including:
anaphylaxis. This is a severe and possibly a life-threatening allergic reaction. Symptoms may include trouble breathing, swelling of your throat or tongue, hives, or difficulty swallowing.
angioedema. This involves swelling of your skin, the layers under your skin, and your mucous membranes (inside your mouth).
Stevens-Johnsons syndrome. This is a rare and serious disorder of your skin and mucous membranes (mouth and nose). It starts with flu-like symptoms and is followed by a painful red rash and blisters.
liver damage. Symptoms may include:
yellowing of your skin and the whites of your eyes (jaundice)
stomach pain and swelling
swelling in your legs and ankles (edema)
itchy skin
dark-colored urine
pale stool or tar-colored stool
constant sleepiness
nausea
vomiting
bruising easily
low blood cell or platelet counts. Symptoms may include infections and bruising or bleeding that doesn’t stop as quickly as normal.
low sodium levels (hyponatremia) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). In SIADH, your body is unable to get rid of excess water by urinating. This leads to lower sodium levels in your blood (hyponatremia), which is dangerous. Symptoms may include:
nausea and vomiting
headache
confusion
loss of energy and fatigue
restlessness and irritability
muscle weakness, spasms, or cramps
seizures
coma

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Tonoflex (Tramadol) 50mg

1. Name of the medicinal product

Tramadol hydrochloride/Paracetamol 37.5 mg/325 mg film-coated tablets

2. Qualitative and quantitative composition

Each film-coated tablet contains 37.5 mg tramadol hydrochloride equivalent to 32.94 mg tramadol and 325 mg paracetamol.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Film-coated tablet.

Tablets are yellow-brown, oval, slightly biconvex.

4. Clinical particulars

4.1 Therapeutic indications

Tramadol hydrochloride/Paracetamol tablets are indicated for the symptomatic treatment of moderate to severe pain.

The use of Tramadol hydrochloride/Paracetamol should be restricted to patients whose moderate to severe pain is considered to require a combination of tramadol and paracetamol (see also section 5.1).

4.2 Posology and method of administration

Posology

Adults and adolescents (12 years and older)

The use of Tramadol hydrochloride/Paracetamol should be restricted to patients whose moderate to severe pain is considered to require a combination of tramadol and paracetamol.

The dose should be individually adjusted according to intensity of the pain and the sensitivity of the individual patient. The lowest effective dose for analgesia should generally be selected.

An initial dose of two tablets of Tramadol hydrochloride/Paracetamol is recommended. Additional doses can be taken as needed, not exceeding 8 tablets (equivalent to 300 mg tramadol hydrochloride and 2600 mg paracetamol) per day.

The dosing interval should not be less than six hours.

Tramadol hydrochloride/Paracetamol should under no circumstances be administered for longer than is strictly necessary (see also section 4.4.). If repeated use or long term treatment with Tramadol hydrochloride/Paracetamol is required as a result of the nature and severity of the illness, then careful, regular monitoring should take place (with breaks in the treatment, where possible), to assess whether continuation of the treatment is necessary.

Paediatric population

The effective and safe use of Tramadol hydrochloride/Paracetamol has not been established in children below the age of 12 years. Treatment is therefore not recommended in this population.

Elderly patients

A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest hepatic or renal insufficiency. In elderly patients over 75 years elimination may be prolonged. Therefore, if necessary the dosage interval is to be extended according to the patient's requirements.

Renal insufficiency/dialysis

Because of the presence of tramadol, the use of Tramadol hydrochloride/Paracetamol is not recommended in patients with severe renal insufficiency (creatinine clearance < 10 ml/min). In cases of moderate renal insufficiency (creatinine clearance between 10 and 30 ml/min), the dosing should be increased to 12-hourly intervals. As tramadol is removed only very slowly by haemodialysis or by haemofiltration, post dialysis administration to maintain analgesia is not usually required.

Hepatic impairment

In patients with hepatic impairment the elimination of tramadol is delayed. In these patients prolongation of dosage intervals should be carefully considered according to the patient's requirements (see section 4.4).

Because of the presence of paracetamol should not be used in patients with severe hepatic impairment (see section 4.3).

Method of administration

Oral use.

Tablets must be swallowed whole, with a sufficient quantity of liquid. They must not be crushed or chewed.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

Acute intoxication with alcohol, hypnotic medicinal products, centrally-acting analgesics, opioids or psychotropic medicinal products.

Tramadol hydrochloride/Paracetamol should not be administered to patients who are receiving monoamine oxidase inhibitors or within two weeks of their withdrawal (see section 4.5).

Severe hepatic impairment.

Epilepsy not controlled by treatment (see section 4.4).

4.4 Special warnings and precautions for use

Warnings

- The maximum dose of 8 tablets of Tramadol hydrochloride/Paracetamol should not be exceeded in adults and adolescents 12 years and older. In order to avoid inadvertent overdose, patients should be advised not to exceed the recommended dose and not to use any other paracetamol (including over the counter) or tramadol hydrochloride containing products concurrently without the advice of a physician.

- In severe renal impairment (creatinine clearance <10 ml/min), Tramadol hydrochloride/Paracetamol is not recommended.

- In patients with severe hepatic impairment Tramadol hydrochloride/Paracetamol should not be used (see section 4.3). The hazards of paracetamol overdose are greater in patients with non-cirrhotic alcoholic liver disease. In moderate cases prolongation of dosage interval should be carefully considered.

- In severe respiratory impairment, Tramadol hydrochloride/Paracetamol is not recommended.

- Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid agonist, tramadol cannot suppress morphine withdrawal symptoms.

- Convulsions have been reported in tramadol-treated patients susceptible to seizures or taking other medications that lower the seizure threshold, especially selective serotonin re-uptake inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local anaesthesia. Epileptic patients controlled by a treatment or patients susceptible to seizures should be treated with Tramadol hydrochloride/Paracetamol only if there are compelling circumstances. Convulsions have been reported in patients receiving tramadol at the recommended dose levels. The risk may be increased when doses of tramadol exceed the recommended upper dose limit.

Precautions for use

Tolerance and physical and/or psychological dependence may develop, even at therapeutic doses. The clinical need for analgesic treatment should be reviewed regularly (see 4.2). In opioid-dependent patients and patients with a history of drug abuse or dependence, treatment should only be for short period and under medical supervision.

Tramadol hydrochloride/Paracetamol should be used with caution in patients with cranial trauma, in patients prone to convulsive disorder, biliary tract disorders, in a state of shock, in an altered state of consciousness for unknown reasons, with problems affecting the respiratory centre or the respiratory function, or with an increased intracranial pressure.

Paracetamol overdosage may cause hepatic toxicity in some patients.

Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal may occur even at therapeutic doses and for short term treatment (see section 4.8). Withdrawal symptoms may be avoided by taper it at the time of discontinuation especially after long treatment periods. Rarely, cases of dependence and abuse have been reported (see section 4.8).

In one study, use of tramadol during general anaesthesia with enflurane and nitrous oxide was reported to enhance intra-operative recall. Until further information is available, use of tramadol during light plans of anaesthesia should be avoided.

4.5 Interaction with other medicinal products and other forms of interaction

Concomitant use is contraindicated with:

- Non-selective MAO Inhibitors

Risk of serotoninergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.

- Selective-A MAO Inhibitors

Extrapolation from non-selective MAO inhibitors, risk of serotoninergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.

- Selective-B MAO Inhibitors

Central excitation symptoms evocative of a serotoninergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state, even coma.

In case of recent treatment with MAO inhibitors, a delay of two weeks should occur before treatment with tramadol

Concomitant use is not recommended with:

- Alcohol

Alcohol increases the sedative effect of opioid analgesics. The effect on alertness can make driving of vehicles and the use of machines dangerous. Avoid intake of alcoholic drinks and of medicinal products containing alcohol.

- Carbamazepine and other enzyme inducers

Risk of reduced efficacy and shorter duration due to decreased plasma concentrations of tramadol.

- Opioid agonists-antagonists (buprenorphine, nalbuphine, pentazocine)

Decrease of the analgesic effect by competitive blocking effect at the receptors, with the risk of occurrence of withdrawal syndrome.

Concomitant use which needs to be taken into consideration

- Tramadol can induce convulsions and increase the potential for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics and other seizure threshold-lowering medicinal products (such as bupropion, mirtazapine, tetrahydrocannabinol), to cause convulsions.

- Concomitant therapeutic use of tramadol and serotonergic drugs such as selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), MAO inhibitors (see section 4.3), tricyclic antidepressants and mirtazapine may cause serotonin toxicity. Serotonin syndrome is likely if when one of the following is observed:

- Spontaneous clonus

- Inducible or ocular clonus with, agitation or diaphoresis

- Tremor and hyperreflexia,

- Hypertonia and body temperature >38°C and inducible or ocular clonus.

Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Treatment depends on the type and severity of the symptoms.

- Other opioid derivatives (including antitussive medicinal products and substitutive treatments), benzodiazepines and barbiturates: increased risk of respiratory depression which can be fatal in cases of overdose.

- Other central nervous system depressants, such as other opioid derivatives (including antitussive drugs and substitutive treatments), barbiturates, benzodiazepines, other anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics, centrally-acting antihypertensive medicinal products, thalidomide and baclofen. These active substances can cause increased central depression. The effect on alertness can make driving of vehicles and the use of machines dangerous.

- Caution should be exercised during concomitant treatment with Tramadol hydrochloride/Paracetamol and coumarin derivatives (e.g. warfarin) due to reports of increased INR with major bleeding and ecchymoses in some patients.

- Other drugs known to inhibit CYP3A4, such as ketoconazole and erythromycin, might inhibit the metabolism of tramadol (N-demethylation) probably also the metabolism of the active O-demethylated metabolite. The clinical importance of such an interaction has not been studied.

- In a limited number of studies the pre- or postoperative application of the antiemetic 5-HT3 antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.

4.6 Fertility, pregnancy and lactation

Pregnancy

Since Tramadol hydrochloride/Paracetamol is a fixed combination of active ingredients including tramadol, it should not be used during pregnancy.

Data regarding paracetamol:

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage.

Data regarding tramadol:

Tramadol should not be used during pregnancy as there is inadequate evidence available to assess the safety of tramadol in pregnant women. Tramadol administered before or during birth does not affect uterine contractility. In neonates it may induce changes in the respiratory rate which are usually not clinically relevant. Long-term treatment during pregnancy may lead to withdrawal symptoms in the newborn after birth, as a consequence of habituation.

Breast-feeding

Since Tramadol hydrochloride/Paracetamol is a fixed combination of active ingredients including tramadol, it should not be used more than once during breast feeding or alternatively, breast-feeding should be discontinued during treatment with tramadol.

Data regarding paracetamol:

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data on paracetamol does not contraindicate it for breast feeding by women using single ingredient medicinal products containing only paracetamol.

Data regarding tramadol:

Approximately 0.1% of the maternal dose of tramadol is excreted in breast milk. In the immediate post-partum period, for maternal oral daily dosage up to 400 mg, this corresponds to a mean amount of tramadol ingested by breast-fed infants of 3% of the maternal weight-adjusted dosage. For this reason tramadol should not be used during lactation or alternatively, breast-feeding should be discontinued during treatment with tramadol. Discontinuation of breast-feeding is generally not necessary following a single dose of tramadol.

Fertility

Post marketing surveillance does not suggest an effect of tramadol on fertility.

Animal studies did not show an effect of tramadol on fertility. No study on fertility was accomplished with the combination of tramadol and paracetamol.

4.7 Effects on ability to drive and use machines

Tramadol hydrochloride may cause drowsiness or dizziness, which may be enhanced by alcohol or other CNS depressants. If affected, the patient should not drive or operate machinery.

4.8 Undesirable effects

Undesirable effects that may occur during treatment with Tramadol hydrochloride/Paracetamol are classified into the following groups in order of frequency:

- very common (≥1/10)

- common (≥1/100 to <1/10)

- uncommon (≥1/1,000 to <1/100)

- rare (≥1/10,000 to <1/1,000)

- very rare (<1/10,000)

- not known (cannot be estimated from the available data)

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The most commonly reported undesirable effects during the clinical trials performed with the paracetamol/tramadol combination were nausea, dizziness and somnolence, observed in more than 10% of the patients.

Frequency of undesirable effects listed by individual organ systems:

Very common

Common

Uncommon

Rare

Very rare

Unknown

Metabolism and nutrition disorders

hypoglycaemia

Psychiatric disorders

confusional state, mood altered, anxiety, nervousness, euphoric mood, sleep disorders

depression, hallucinations, nightmares, amnesia

drug dependence

abuse*

Nervous system disorders

dizziness, somnolence

headache, trembling

involuntary muscular contractions, paraesthesia

ataxia, convulsions, syncope

Eye disorders

blurred vision

Ear and labyrinth disorders

tinnitus

Cardiac disorders

palpitations, tachycardia, arrythmia

Vascular disorders

hypertension, hot flush

Respiratory, thoracic and mediastinal disorders

dyspnoea

Gastrointestinal disorders

nausea

vomiting, constipation, dry mouth, diarrhoea abdominal pain, dyspepsia, flatulence

dysphagia, melaena.

Skin and subcutaneous tissue disorders

hyperhidrosis, pruritus

dermal reactions (e.g. rash, urticaria)

Renal and urinary disorders

albuminuria, micturition disorders (dysuria and urinary retention).

General disorders and administration site conditions

chills, chest pain

Investigations

transaminases increase

*Reported in post marketing surveillance.

Although not observed during clinical trials, the occurrence of the following undesirable effects known to be related to the administration of tramadol or paracetamol cannot be excluded:

Tramadol

- Postural hypotension, bradycardia, collapse (tramadol).

- Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect, including elevation of prothrombin times.

- Rare cases: allergic reactions with respiratory symptoms (e.g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis.

- Rare cases: changes in appetite, motor weakness, and respiratory depression.

- Psychic side-effects may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of medication). These include changes in mood, (usually elation occasionally dysphoria), changes in activity (usually suppression occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision behaviour perception disorders).

- Worsening of asthma has been reported though a causal relationship has not been established.

- Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms. Other symptoms that have very rarely been seen if tramadol hydrochloride is discontinued abruptly include: panic attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and unusual CNS symptoms.

Paracetamol

- Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

- There have been several reports that suggest that paracetamol may produce hypoprothrombinemia when administered with warfarin-like compounds. In other studies, prothrombin time did not change.

- Very rare cases of serious skin reactions have been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9 Overdose

Tramadol hydrochloride/Paracetamol is a fixed combination of active ingredients. In case of overdose, the symptoms may include the signs and symptoms of toxicity of tramadol or paracetamol or of both these active ingredients.

Symptoms of overdose from tramadol

In principle, on intoxication with tramadol, symptoms similar to those of other centrally acting analgesics (opioids) are to be expected. These include in particular, miosis, vomiting, cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory depression up to respiratory arrest.

Symptoms of overdose from paracetamol

An overdose is of particular concern in young children. Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalophathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Liver damage is possible in adults who have taken 7.5-10 g or more of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Emergency treatment

- Transfer immediately to a specialised unit.

- Maintain respiratory and circulatory functions.

- Prior to starting treatment, a blood sample should be taken as soon as possible after overdose in order to measure the plasma concentration of paracetamol and tramadol and in order to perform hepatic tests.

- Perform hepatic tests at the start (of overdose) and repeat every 24 hours. An increase in hepatic enzymes (ASAT, ALAT) is usually observed, which normalizes after one or two weeks.

- Empty the stomach by causing the patient to vomit (when the patient is conscious) by irritation or gastric lavage.

- Supportive measures such as maintaining the patency of the airway and maintaining cardiovascular function should be instituted; naloxone should be used to reverse respiratory depression; fits can be controlled with diazepam.

- Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration. Therefore treatment of acute intoxication with Tramadol hydrochloride/Paracetamol with haemodialysis or haemofiltration alone is not suitable for detoxification.

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention and any adult or adolescent who had ingested around 7.5 g or more of paracetamol in the preceding 4 hours or any child who has ingested ≥150 mg/kg of paracetamol in the preceding 4 hours should undergo gastric lavage. Paracetamol concentrations in blood should be measured later than 4 hours after overdose in order to be able to assess the risk of developing liver damage (via the paracetamol overdose nomogram). Administration of oral methionine or intravenous N-acetylcysteine (NAC) which may have a beneficial effect up to at least 48 hours after the overdose, may be required. Administration of intravenous N-acetylcysteine (NAC) is most beneficial when initiated within 8 hours of overdose ingestion. However, NAC should still be given if the time to presentation is greater than 8 hours after overdose and continued for a full course of therapy. NAC treatment should be started immediately when massive overdose is suspected. General supportive measures must be available.

Irrespective of the reported quantity of paracetamol ingested, the antidote for paracetamol, NAC, should be administered orally or intravenously, as quickly as possible, if possible, within 8 hours following the overdose.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: other opioids, tramadol, combinations, ATC code: N02AX52.

Analgesics

Tramadol is an opioid analgesic that acts on the central nervous system. Tramadol is pure non selective agonists of the μ, δ, and κ opioid receptors with a higher affinity for the µ receptors. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal reuptake of noradrenaline and enhancement of serotonin release. Tramadol has an antitussive effect. Unlike morphine, a broad range of analgesic doses of tramadol has no respiratory depressant effect. Similarly, the gastro-intestinal motility is not modified. The cardiovascular effects are generally slight. The potency of tramadol is considered to be one-tenth to one-sixth that of morphine.

Mechanism of action

The precise mechanism of the analgesic properties of paracetamol is unknown and may involve central and peripheral effects.

Tramadol hydrochloride/Paracetamol is positioned as a step II analgesic in the WHO pain ladder and should be utilised accordingly by the physician.

5.2 Pharmacokinetic properties

Tramadol is administered in racemic form and the [-] and [+] forms of tramadol and its metabolite M1, are detected in the blood. Although tramadol is rapidly absorbed after administration, its absorption is slower (and its half-life longer) than that of paracetamol.

After a single oral administration of a tramadol/paracetamol (37.5 mg/325 mg) tablet, peak plasma concentrations of 64.3/55.5 ng/ml [(+)-tramadol/(-)-tramadol] and 4.2 µg/ml (paracetamol) are reached after 1.8 h [(+)-tramadol/(-)-tramadol] and 0.9 h (paracetamol) respectively. The mean elimination half-lives t1/2 are 5.1/4.7 h [(+)-tramadol/(-)-tramadol] and 2,5 h (paracetamol).

During pharmacokinetic studies in healthy volunteers after single and repeated oral administration of Tramadol hydrochloride/Paracetamol, no clinical significant change was observed in the kinetic parameters of each active ingredient compared to the parameters of the active ingredients used alone.

Absorption

Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a single 100 mg dose is approximately 75%. After repeated administration, the bioavailability is increased and reaches approximately 90%.

After administration of Tramadol hydrochloride/Paracetamol, the oral absorption of paracetamol is rapid and nearly complete and takes place mainly in the small intestine. Peak plasma concentrations of paracetamol are reached in one hour and are not modified by concomitant administration of tramadol.

The oral administration of Tramadol hydrochloride/Paracetamol with food has no significant effect on the peak plasma concentration or extent of absorption of either tramadol or paracetamol so that Tramadol hydrochloride/Paracetamol can be taken independently of meal times.

Distribution

Tramadol has a high tissue affinity (Vd,β=203 ± 40 l). It has a plasma protein binding of about 20%.

Paracetamol appears to be widely distributed throughout most body tissues except fat. Its apparent volume of distribution is about 0.9 l/kg. A relative small portion (~20%) of paracetamol is bound to plasma proteins.

Biotransformation

Tramadol is extensively metabolized after oral administration. About 30% of the dose is excreted in urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

Tramadol is metabolised through O-demethylation (catalysed by the enzyme CYP2D6) to the metabolite M1, and through N-demethylation (catalysed by CYP3A) to the metabolite M2. M1 is further metabolised through N-demethylation and by conjugation with glucuronic acid. The plasma elimination half-life of M1 is 7 hours. The metabolite M1 has analgesic properties and is more potent than the parent drug. The plasma concentrations of M1 are several-fold lower than those of tramadol and the contribution to the clinical effect are unlikely to change on multiple dosing.

Paracetamol is principally metabolized in the liver through two major hepatic routes: glucuronidation and sulphation. The latter route can be rapidly saturated at doses above the therapeutic doses. A small fraction (less than 4%) is metabolized by cytochrome P450 to an active intermediate (the N-acetyl benzoquinoneimine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and excreted in urine after conjugation to cysteine and mercapturic acid. However, during massive overdose, the quantity of this metabolite is increased.

Elimination

Tramadol and its metabolites are eliminated mainly by the kidneys.

The half-life of paracetamol is approximately 2 to 3 hours in adults. It is shorter in children and slightly longer in the newborn and in cirrhotic patients. Paracetamol is mainly eliminated by dose-dependent formation of glucuro- and sulpho-conjugate derivatives. Less than 9% of paracetamol is excreted unchanged in urine. In renal insufficiency, the half-life of both compounds is prolonged.

5.3 Preclinical safety data

No preclinical study has been performed with the fixed combination (tramadol and paracetamol) to evaluate its carcinogenic or mutagenic effects or its effects on fertility.

No teratogenic effect that can be attributed to the medicine has been observed in the progeny of rats treated orally with the combination tramadol/paracetamol.

The combination tramadol/paracetamol has proven to be embryotoxic and foetotoxic in the rat at materno-toxic dose (50/434 mg/kg tramadol/paracetamol), i.e., 8.3 times the maximum therapeutic dose in man. No teratogenic effect has been observed at this dose. The toxicity to the embryo and the foetus results in a decreased foetal weight and an increase in supernumerary ribs. Lower doses, causing less severe materno-toxic effect (10/87 and 25/217 mg/kg tramadol/paracetamol) did not result in toxic effects in the embryo or the foetus.

Results of standard mutagenicity tests did not reveal a potential genotoxic risk for tramadol in man.

Results of carcinogenicity tests do not suggest a potential risk of tramadol for man.

Animal studies with tramadol revealed, at very high doses, effects on organ development, ossification and neonatal mortality, associated with maternotoxicity. Fertility reproductive performance and development of offspring were unaffected. Tramadol crosses the placenta. No effect on fertility has been observed after oral administration of tramadol up to doses of 50 mg/kg in the male rat and 75 mg/kg in the female rat.

Extensive investigations showed no evidence of a relevant genotoxic risk of paracetamol at therapeutic (i.e. non-toxic) doses.

Long-term studies in rats and mice yielded no evidence of relevant tumorigenic effects at non-hepatotoxic dosages of paracetamol.

Animal studies and extensive human experience to date yield no evidence of reproductive toxicity.

6. Pharmaceutical particulars

6.1 List of excipients

Tablet core:

Pregelatinised maize starch

Sodium starch glycolate (type A)

Microcrystalline cellulose (E460)

Magnesium stearate (E572)

Film-coating:

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol 400

Yellow iron oxide (E172)

Polysorbate 80

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Blister (PVC/PVDC white foil, aluminium foil): 2 film-coated tablets (blisters with 2 tablets) or 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 film-coated tablets (blisters with 10 tablets), in a box.

Child-resistant blister (PVC/PVDC white foil, paper/aluminium foil): 2 film-coated tablets (blisters with 2 tablets) or 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 film-coated tablets (blisters with 10 tablets), in a box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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Opinor 0.3mg

OPINOR 0.3mg

Generic Name: Buprenorphine

Buprenorphine is used to treat opioid dependence (addiction to opioid drugs, including heroin and narcotic painkillers). Buprenorphine is in a class of medications called opioid partial agonist-antagonists, and naloxone is in a class of medications called opioid antagonists. Buprenorphine alone and the combination of buprenorphine and naloxone prevent withdrawal symptoms when someone stops taking opioid drugs by producing similar effects to these drugs.

How should this medicine be used?
Buprenorphine and the combination of buprenorphine and naloxone come as sublingual tablets to taken under the tongue. They are usually taken once a day. To help you remember to take buprenorphine or buprenorphine and naloxone, take it around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take buprenorphine or buprenorphine and naloxone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
You will start your treatment with buprenorphine, which you will take in the doctor’s office. Your doctor will start you on a low dose of buprenorphine and will increase your dose for several days before switching you to buprenorphine and naloxone. Your doctor may increase or decrease your buprenorphine and naloxone dose until the medication works properly.
Place the tablets under your tongue until they melt. This should take 2 to 10 minutes. If you are taking more than two tablets, either place them all under your tongue at the same time or place them under your tongue 2 at a time. Do not chew the tablets or swallow them whole.
Do not stop taking buprenorphine and naloxone without talking to your doctor. Stopping buprenorphine and naloxone too quickly can cause withdrawal symptoms. Your doctor will tell you when and how to stop taking buprenorphine and naloxone.

Before taking buprenorphine:

• Tell your doctor and pharmacist if you are allergic to buprenorphine, naloxone, or any other medications.
• Do not take antidepressants (‘mood elevators’), narcotic pain killers, sedatives, sleeping pills, or tranquilizers while taking buprenorphine or buprenorphine and naloxone.
• Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: acetaminophen (Tylenol, others); antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole (Nizoral); carbamazepine (Tegretol); cholesterol-lowering medications (statins); cimetidine (Tagamet); clarithromycin (Biaxin); cyclosporine (Neoral, Sandimmune); danazol (Danocrine); delavirdine (Rescriptor); dexamethasone (Decadron); diltiazem (Cardizem, Dilacor, Tiazac); erythromycin (E.E.S., E-Mycin, Erythrocin); ethosuximide (Zarontin);fluoxetine (Prozac, Sarafem); fluvoxamine (Luvox); HIV protease inhibitors such as indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir); iron products; isoniazid (INH, Nydrazid); medications for anxiety, mental illness, and seizures; methotrexate (Rheumatrex); metronidazole (Flagyl);nefazodone (Serzone); niacin (nicotinic acid); oral contraceptives (birth control pills); phenobarbital (Luminal, Solfoton); phenytoin (Dilantin); rifabutin (Mycobutin); rifampin (Rifadin, Rimactane); troglitazone (Rezulin); troleandomycin (TAO); verapamil (Calan, Covera, Isoptin, Verelan); and zafirlukast (Accolate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• Tell your doctor if you drink large amounts of alcohol and if you have or have ever had adrenal problems such as Addison’s disease; benign prostatic hypertrophy (BPH, enlargement of the prostate gland); difficulty urinating; head injury; hallucinations (seeing things or hearing voices that do not exist); a curve in the spine that makes it hard to breathe; gallbladder disease; stomach conditions; and thyroid, kidney, liver, or lung disease.
• Tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking buprenorphine or buprenorphine and naloxone, call your doctor.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking buprenorphine or buprenorphine and naloxone.
• You should know that buprenorphine or buprenorphine and naloxone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• Remember that alcohol can add to the breathing difficulties that can be caused by this medication.
• You should know that buprenorphine or buprenorphine and naloxone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking buprenorphine or buprenorphine and naloxone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

side effects:

• Headache
• Stomach pain
• Constipation
• Vomiting
• Difficulty falling asleep or staying asleep
• Sweating
• Hives
• Skin Rash
• Itching
• Difficulty breathing or swallowing
• Slowed Breathing
• Upset Stomach
• Extreme Tiredness
• Unusual bleeding or bruising
• lack of energy
• Loss of appetite
• Pain in the upper right part of the stomach
• Yellowing of the skin or eyes
• Flu-like symptoms

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Buprenorphine or buprenorphine and naloxone can be a target for people who abuse prescription medications or street drugs. Keep your medication in a safe place to protect from theft. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

What other information:
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body’s response to buprenorphine and naloxone.
In case of an emergency, you or a family member should tell the treating doctor or emergency room staff that you are taking buprenorphine or buprenorphine and naloxone.
Do not inject buprenorphine or sublingual tablets. Severe reactions may happen, including withdrawal symptoms.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

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Testonon (Testosterone Compound) 250mg/1ml by zafa

TESTONON

Characteristics:

TESTONON is an androgenic preparation for intramuscular administration containing four different esters of the natural hormone testosterone. Testosterone propionate has a rapid onset and a short duration of action. Testosterone phenylpropionate and isocaproate have a less rapid onset and a long duration of action. By combining these testosterone esters, the action of TESTONON ‘’ starts shortly after injection and is maintained for about three weeks.

TESTONON is generally well tolerated and has no adverse effect on the liver.

Indications:

Testosterone replacement therapy in male hypogonadal disorders, for example:
-    after castration
-    eunuchoidism
-    hypopituitarism
-    endocrine impotence
-    male climacteric symptoms such as decreased libido and decreased mental and physical activity
-    certain types of infertility due to disorders of spermatogenesis;
Moreover, testosterone therapy may be indicated in osteoporosis due to androgen deficiency.

Dosage:

In general, dosage should be adjusted according to the response of the individual patient. Usually, one injection of 1 ml per three weeks is adequate or as prescribed by the physician.

Administration:

TESTONON should be administered by deep intramuscular injection.

Contra-indications:

-    Known or suspected prostatic or mammary carcinoma.

Warnings and precautions:

-    If androgen associated adverse reactions occur, treatment should be interrupted and after disappearance of the symptoms, should be resumed at a lower dosage.

-    Patients with latent or overt cardiac failure, renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions) should be monitored, since androgens may occasionally induce salt and fluid retention.

-    Androgens should be used cautiously in prepubertal boys to avoid premature epiphyseal closure or precocious sexual development.

-    Oligosperma and decreased ejaculatory volume.
-    A decrease in protein-bound iodine (PBI) may occur, but this has no clinical significance.

Adverse reactions:

The following adverse reactions have been associated with androgen therapy:

-    Priapism and other signs of excessive sexual stimulation.

-    In prepubertal boys, precocious sexual development, an increased frequency of erections, phallic enlargement and premature epiphyseal closure.

-    Water and salt retention.
-    Oligosperma and decreased ejaculatory volume.

Instructions:

To be sold on the prescription of a registered medical practitioner only.

Store at 8-30°C. Protect from light.
Keep out of the reach of children.

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Sustanon 250mg/1ml by organon

Product Description

Brand Name:

Sustanon® ‘250’

Injection

(Testosterone Propionate)

(Testosterone Phenylpropionate)

(Testosterone Isocaproate)

(Testosterone Decanoate)

By:  Organon

Presentation:

Box of 1 x 1 ml ampoule

Composition:

Each ml of the oily solution contains:

testosterone propionate (Eur. P.)………… 30 mg

testosterone phenylpropionate (B.P.)……. 60 mg

testosterone isocaproate (B.P.)…………... 60 mg

testosterone decanoate (B.P.)……………100 mg

Characteristics:

Sustanon ‘250’ is an androgenic preparation for intramuscular administration containing four different esters of the natural hormone testosterone. Testosterone propionate has a rapid onset and a short duration of action. Testosterone phenylpropionate and isocaproate have a less rapid onset and a long duration of action. By combining these testosterone esters, the action of Sustanon ‘250’ starts shortly after injection and is maintained for about three weeks.

Sustanon ‘250’ is generally well tolerated and has no adverse effect on the liver.

Indications:

Testosterone replacement therapy in male hypogonadal disorders, for example:

-    after castration 

-    eunuchoidism 

-    hypopituitarism 

-    endocrine impotence 

-    male climacteric symptoms such as decreased libido and decreased mental and physical activity 

-    certain types of infertility due to disorders of spermatogenesis; 

Moreover, testosterone therapy may be indicated in osteoporosis due to androgen deficiency.

Dosage:

In general, dosage should be adjusted according to the response of the individual patient. Usually, one injection of 1 ml per three weeks is adequate or as prescribed by the physician.

Administration:

Sustanon ‘250’ should be administered by deep intramuscular injection.

Contra-indications:

-    Known or suspected prostatic or mammary carcinoma. 

Warnings and precautions:

-    If androgen associated adverse reactions occur, treatment should be interrupted and after disappearance of the symptoms, should be resumed at a lower dosage. 

-    Patients with latent or overt cardiac failure, renal dysfunction, hypertension, epilepsy or migraine (or a history of these conditions) should be monitored, since androgens may occasionally induce salt and fluid retention. 

-    Androgens should be used cautiously in prepubertal boys to avoid premature epiphyseal closure or precocious sexual development. 

-    Oligosperma and decreased ejaculatory volume. 

-    A decrease in protein-bound iodine (PBI) may occur, but this has no clinical significance. 

Adverse reactions:

The following adverse reactions have been associated with androgen therapy:

-    Priapism and other signs of excessive sexual stimulation. 

-    In prepubertal boys, precocious sexual development, an increased frequency of erections, phallic enlargement and premature epiphyseal closure. 

-    Water and salt retention. 

-    Oligosperma and decreased ejaculatory volume. 

Instructions:

To be sold on the prescription of a registered medical practitioner only.

Store at 8-30°C. Protect from light.

Keep out of the reach of children.

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