Buy Generic Grifulvin (Griseofulvin) 250 mg online

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Most popular brand: Grifulvin
Active ingredient: Griseofulvin
Available dosage forms: 250 mg

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Griseofulvin general information

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Griseofulvin (Griseofulvin): instruction, and the use of a formula

The nosological classification (ICD – 10)

Code CAS

Feature substance Griseofulvin

The antifungal agent. An antibiotic produced by molds Penicillium nigricans (griseofulvum). White or white with a yellowish tinge naimelchayshy crystalline powder with low specific (mushroom) odor. Practically insoluble in water and petroleum ether, slightly soluble in ethanol, methanol, acetone, benzene, ethyl acetate, acetic acid. Solubility in dimethylformamide at 25 ° C: 12 – 14 g / 100 ml. Stable at high temperatures, including autoclaving. Molecular weight 352,77.

Pharmacology

Mode of action -. Antifungal, fungistatic

fungistatic action associated with the effect on microtubule proteins fungal cell, resulting in the rupture of mitotic spindle stop structures and mitotic division of cells in metaphase fungus, inhibits protein synthesis, cell wall formation gives from chitin-containing fungi. Has b & oacute; greater tropism for the affected tissues: selectively accumulates in the precursor of skin keratinocytes, hair and nails, is closely associated with the newly formed keratin, providing it with high resistance to fungal invasion (thus preventing fungal infection of new cells are formed). Gradually containing keratin exfoliated structure. Healing occurs after the complete replacement of the infected keratin, so the therapeutic effect develops slowly.

Active against dermatomitsetami, including Trichophyton ( Trichophyton rubrum . Trichophyton tonsurans . Trichophyton mentagrophytes . Trichophyton interdigitalis . Trichophyton verrucosum . Trichophyton sulphureum . Trichophyton menginii . Trichophyton gallinae . Trichophyton schoenleini . Trichophyton crateriforme ), Microsporum ( Microsporum audouinii . Microsporum canis . Microsporum gypseum ), Epidermophyton ( Epidermophyton floccosum ). Fungistatic concentration for most sensitive species of fungi griseofulvin is 0,5 – 3 mg / ml. Yeast fungus (genus Candida ) and fungi resistant to griseofulvin. Antibacterial activity is not.

When administered griseofulvin absorption depends on the dispersion of its crystals: the magnitude of the suction microcrystalline form varies from 25 to 70%, ultramikrokristallicheskaya form almost completely absorbed. Absorption from the gastrointestinal tract is very much varies from person to person, mainly because of – the insolubility of the substance in the water environment of the upper GI tract. C _max is 0,5 & ndash in the blood of adults on an empty stomach after ingestion of 0.5 g of griseofulvin; 2.0 ug / ml and is reached after 4 hours should be noted that in some patients, there is a trend. to the creation of low levels of substances in the blood, regardless of time. This may explain the unsatisfactory therapeutic effect in some patients. The bioavailability is increased in most patients when co-administered with fatty food. After ingestion accumulate in the stratum corneum and its appendages, and in the liver, adipose tissue, skeletal muscle. Minor amounts fall within the fluids and other body tissues. The biotransformation occurs in the liver, the major metabolite ; 6 – metilgrizeofulvin and glucuronide derivative. T _1/2 ; about 24 hours, no change in renal failure. Return with faeces (36% ; in unchanged form) and in urine (less than 1% unchanged).

When applied topically, griseofulvin has little effect.

Toxicology animals

The long-term studies in animals treated with griseofulvin with food (0,5 – 2,5% of feed), several strains of mice, especially in males, noted the formation of hepatocellular carcinomas. This effect was higher with griseofulvin particle size finer. P / incorporation of relatively lower doses of griseofulvin 1 time per week for the first three weeks of life is also led to the formation of hepatocellular carcinomas in mice.

The tumors of the thyroid gland (usually adenomas, but sometimes it ; carcinoma) developed in male rats treated with griseofulvin with food (2.0, 1.0, and 0.2% of the feed), and in female rats at 2 times greater griseofulvin content in food. In experiments on other species carcinogenic effects were found.

The study of subacute toxicity when administered into griseofulvin caused hepatocellular necrosis in mice, but this effect was not observed in other species. In laboratory animals, treated with griseofulvin, porphyrin metabolism disorders were observed. Griseofulvin provided kolhitsinopodobny effect on mitosis and contributed to the development of skin tumors in laboratory animals at methylcholanthrene induction.

Application of the substance Griseofulvin

Skin fungal infections, scalp and nails: favus, trihofitia, mikrosporiya scalp mikrosporiya smooth skin, beard and mustache ringworm, athlete’s smooth skin, jock itch, onychomycosis.

Contraindications

Hypersensitivity, porphyria, systemic lupus erythematosus, lupus-like syndrome, systemic blood diseases, leukopenia, organic liver and kidney disease, hepatocellular insufficiency, cancer.

Restrictions on the use

Children under 2 years of age (efficacy and safety have not been determined).

Application of pregnancy and breastfeeding

There is evidence of teratogenic and embryotoxic effects of griseofulvin in animals (for oral administration in pregnant rats was reported the presence in the litter pups with multiple impairments). It is shown that griseofulvin suppresses spermatogenesis in rats, although studies in humans is unknown. Experiments on dogs showed that griseofulvin may cause adverse effects in the offspring.

is contraindicated in pregnancy (griseofulvin crosses the placenta, adequate and well-controlled studies have been conducted in pregnant women). Since 1977, it reported two cases of birth of conjoined twins in patients treated with griseofulvin in the I trimester of pregnancy. If the pregnancy during therapy with griseofulvin, you must inform the patient about the potential risk to the fetus.

The use of breast-feeding is not recommended (it is not known whether griseofulvin passes into breast milk gets). Adequate data are not available.

Side effects of substance Griseofulvin

From the digestive tract: nausea, vomiting, dry mouth, diarrhea, abdominal pain, oral candidiasis, elevated liver enzymes, jaundice, hepatitis.

From the nervous system and sensory organs: headache, dizziness, excessive fatigue or weakness, insomnia, peripheral neuropathy, paresthesia of extremities, incoordination, confusion, disorientation, confusion, depression, disturbance taste sensitivity.

From the cardio – vascular system and blood (blood, hemostasis): granulocytopenia, agranulocytosis, leukopenia.

Allergic reactions: rash, pruritus, urticaria, angioedema, photosensitivity, lupus-like syndrome, erythema multiforme, topical epidermal necrolysis (Lyell’s syndrome).

Interaction

Griseofulvin induces microsomal enzymes of the liver and thus can enhance the metabolism in the liver and therefore weaken the activity of anticoagulants (requires monitoring of PV. Dosage adjustment may be necessary anticoagulant), oral hypoglycemic agents (control of blood glucose, possible dose adjustment antidiabetic funds), oral contraceptives estrogensoderjath, theophylline (monitor its concentration in the blood with possible dose adjustments). Inductors microsomal enzymes (including barbiturates, rifampicin) may increase the metabolism of griseofulvin and reduce its fungistatic activity. It enhances the effect of ethanol.

interaction with cyclosporine

The combined application of griseofulvin and cyclosporine can vary unpredictably effect (sharing requires caution).
Reported few instances of interaction between cyclosporine and griseofulvin. The mechanism of this interaction is not clear. Thus, in one study, there was a reduction in the patient’s cyclosporin level about 2 times when assigning griseofulvin 500 mg / day. despite a 70% increase in the dose of cyclosporine. When, after 16 weeks of griseofulvin canceled, cyclosporine serum levels increased.

Stockley’s drug interactions / Ed. by I.H. Stockley. – 6th ed. – London – Chicago, Pharmaceutical Press. – 2002. -. P.619

Dosing and Administration

inside (during or immediately after a meal), in one or more steps. The daily dose for adult ; 500 mg (for severe fungal infections, increase the dose), for children ; 10 mg / kg. The highest daily dose of ; 1, the duration of treatment depends on the infection and on the keratin thickness at the site of infection, and is as follows: with the defeat of the scalp ; 4 – 6 weeks. Body ; 2 – 4 weeks. Stop ; 4 – 8 weeks. fingers ; at least 4 months, toes ; at least 6 months.

Precautions substance Griseofulvin

Prior to initiating therapy with griseofulvin is necessary to identify the type of fungus that caused the infection. Griseofulvin is not suitable for prophylactic use, it is not used to treat mild infections, for which purpose only enough antifungals for topical use. Griseofulvin is not effective for the treatment of bacterial infections, candidiasis, histoplasmosis, actinomycosis, sporotrichosis, chromomycosis, coccidioidomycosis, blastomycosis North, cryptococcosis, nocardiosis, and tinea versicolor.

If you have a diet low in fat, it is necessary to take griseofulvin with 1 tablespoon of vegetable oil. During treatment, you can not drink alcoholic beverages.

With the development of granulocytopenia griseofulvin treatment should be discontinued. Because therapy is prolonged,

requires periodic monitoring of liver function, kidney, hematopoietic.

In elderly patients due to age-related changes in liver function may increase the risk of hepatotoxicity (requires strict clinical and laboratory control).

During therapy with griseofulvin, patients should avoid exposure to direct sunlight and UV radiation.

During the period of treatment and for 6 months should use effective contraceptive measures after the men and women of childbearing age (negative impact on the reproductive function in both men and women).

Do not appoint outpatient drivers transport, as well as people whose professional activity requires quick reaction and attention.