فئة علاجية: Antifungals

Chemical Composition: Each vaginal Suppository contains Metronidazol 500 mg, Miconazole Nitrate 100mg.

Excipients: Hydrogenated vegetable oil,Aerosil.

PHARMACODYNAMICS:

This product contains miconazole for antifungal, metronidazole for antibacterial and antitrichomonal effects. Miconazole nitrate which is an antifungal has a wide spectrum of activity and is particularly effective against pathogen fungi including Candida albicans. In addition, miconazole nitrate is effective against Gram (+) bacteria. Metronidazole is an antibacterial and antiprotozoal agent that is effective against Gardenella vaginalis and against anaerobic bacteria including anaerobic streptococci and Trichomonas vaginalis.

PHARMACOKINETICS:

Absorption of miconazole nitrate through the intravaginal route is very low (approximately 1.4% of dose). Bioavailability of metronidazole by this route is 20% compared to the oral route. Miconazole nitrate cannot be detected in plasma after vaginal application of the suppository. Steady state level of metronidazole in plasma reaches 1.6 – 7.2 μg/ml. Metronidazole is metabolized in the liver. The hydroxyl- metabolite is effective. The half-life of metronidazole is 6- 11 hours. Approximately 20% of the dose is excreted unchanged in urine.

INDICATIONS:

Metronidazole + Miconazole nitrate vaginal suppository is used for local treatment of vaginalis infection with the involvement of certain fungi (eg Candida albicans), some bacteria and other pathogenic organisms (Trichomonas vaginalis). CONTRAINDICATIONS:

Metronidazole + Miconazole nitrate should not be used in the following cases: Hypersensitivity to any of the ingredients of the suppository.

Pregnancy (particularly in the first 3 months).

Severe problems with liver (liver function disorders including metabolic disease called “porphyria”.

Diseases of the nervous system.
Disturbances in the production of blood.

WARNINGS / PRECAUTIONS:

Alcohol should not be taken during the therapy and for at least 24-48 hours after the end of course of treatment because of the possibility of increased alcohol incompatibility.

The suppository should not be used together with the contraceptive diaphragms and condoms since the ovule base may affect the rubber, which may possibly break. Pregnancy and Lactation:

After the first three months of pregnancy, Metronidazole + Miconazole nitrate suppository can be used when considered essential by the doctor, but must be used under observation.

Breastfeeding is not allowed while using Metronidazole + Miconazole nitrate, since active ingredients pass into the milk. Breastfeeding may be started again 24-48 hours after the treatment is finished.

SIDE EFFECTS:

Vaginal Disorders: Vaginal irritation (burning, itching). Owing to the inflammation of the vaginal mucosa in vaginitis, vaginal irritation can be seen after the administration of the first suppository or towards the 3rd day of the treatment. These complaints disappear quickly when the treatment continues. If there is severe irritation, the physician should be informed because it may be necessary to stop the treatment.

Vaginal products should be avoided

Check with the doctor before use if vaginal yeast infections are frequent (such as once a

month or 3 in 6 months), it could be serious underlying medical cause, including (diabetes or a weakened immune system) or if the vaginal itching and discomfort is for the first time. Stop use and check with the doctor if

Symptoms do not get better in 3 days

Symptoms last more than 7 days

If the patient gets a rash or hives, abdominal pain, fever, chills, nausea, vomiting, or foul- smelling vaginal discharge, it could be more serious condition.

Laboratory Tests:

If there is a lack of response to Miconazole Vaginal Suppositories, appropriate microbiological studies should be repeated to confirm the diagnosis and rule out other pathogens. DRUG INTERACTION:

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after vaginal application, clinically interactions occur very rarely.

In patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored because bleeding or bruising may occur

The effects and side effects of other drugs metabolized by CYP2C9 (e.g. oral hypoglycemics and phenytoin) and also CYP3A4 (e.g., simvastatin and lovastatin and calcium channel blockers such as dihydropyridines and verapamil), when co-administered with miconazole, can be increased and caution should be exercised.

Pregnancy and lactation:

Pregnancy: Although intravaginal absorption is limited, miconazole should be used in the first trimester of pregnancy only if the potential benefits outweigh the possible risks.

Breastfeeding: It is not known whether miconazole nitrate is excreted in human milk. Caution should be exercised when using miconazole during breastfeeding.

ADVERSE REACTIONS:

Very common: Genital pruritus, vaginal burning sensation, vulvovaginal discomfort.

Common: Rash, Dysmenorrhea.

Uncommon: pruritic rash, urticaria, headaches, itching or irritation, cramping.

Rare: hives.

OVERDOSE:

Symptoms: miconazole vaginal cream and ovules are intended for local application and not for oral use. In case of accidental ingestion, no problems are expected.

Treatment: In the event of accidental ingestion of large quantities, appropriate supportive care should be used.

STORAGE CONDITIONS:

Vaginal cream: Store at temperature between (15-25) °C

Vaginal suppositories: Store at temperature between (15-25) °C.

Keep out of reach of children.

PACKAGE:

Vaginal cream:

Aluminium tube contains 70 g MECOZALEN vaginal cream with an applicator/carton box. Vaginal Suppositories:

Carton MECOZALEN box contains 3 vaginal Suppositories.

Carton MECOZALEN box contains 6 vaginal Suppositories.

Miconazole Nitrate 2% + Hydrocortisone (Acetate) 1%

Topical (Cream, Ointment)

COMPOSITION:

Each 100 g of MECOZALEN CORT (cream, ointment) contains: Miconazole nitrate 2g, Hydrocortisone (as Hydrocortisone acetate) 1 g.

EXCIPIENTS:

MECOZALEN CORT cream: Cetylstearyl Alcohol with Ethylene Oxide, Cetostearyl Alcohol, Liquid Paraffin, Benzoic Acid, Disodium Edetate, Butylated Hydroxyanisole, Sodium Hydroxide Solution, Purified Water.

MECOZALEN CORT ointment: Polyethylene, Liquid Paraffin gel.

INDICATIONS:

For the topical treatment of inflamed dermatosis where infection by susceptible organisms and inflammation co-exist, e.g. intertrigo and infected eczema.

Moist or dry eczema or dermatitis including atopic eczema, primary irritant or contact allergic eczema or seborrhoeic eczema including that associated with acne.

Intertriginous eczema including inflammatory intertrigo, perianal and genital dermatitis.

Organisms which are susceptible to miconazole are dermatophytes and pathogenic yeasts (e.g. Candida spp.). Also many Gram- positive bacteria including most strains of Streptococcus and Staphylococcus.

DOSAGE AND ADMINISTRATION:

For topical administration.

Apply MECOZALEN CORT two or three times a day to the affected area, rubbing in gently until it has been absorbed by the skin. Because of its corticosteroid content avoid long-term treatment with MECOZALEN CORT. Once the inflammatory symptoms have disappeared (after about 7 days),

treatment can be continued where necessary with MECOZALEN CORT (miconazole nitrate 2%). Treatment should be continued without interruption until the lesion has completely disappeared (usually after 2 to 5 weeks).

If after about 7 days’ application, no improvement has occurred, cultural isolation of the offending organism should be followed by appropriate local or systemic antimicrobial therapy.

The same dosage applies to both adults and children.

Elderly

Natural thinning of the skin occurs in the elderly, hence corticosteroids should be used sparingly and for short periods of time.

Pediatrics

In infants and children, caution is advised when MECOZALEN CORT is applied to extensive surface areas or under occlusive dressings including baby napkins (diapers). In infants, long term continuous topical corticosteroid therapy should be avoided. CONTRAINDICATIONS:

– True hypersensitivity to miconazole/miconazole nitrate, other imidazole derivatives, hydrocortisone or to any of the excipients. – Tubercular or viral infections of the skin or those caused by Gram-negative bacteria.

WARNINGS AND PRECAUTIONS:

– When MECOZALEN CORT is used by patients taking oral anticoagulants, the anticoagulant effect should be carefully monitored. Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with MECOZALEN CORT and with other miconazole topical formulations. If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued.

– MECOZALEN CORT must not come into contact with the mucosa of the eyes.

– As with any topical corticosteroid, caution is advised with infants and children when MECOZALEN CORT is to be applied to extensive surface areas or under occlusive dressings including baby napkins; similarly, application to the face should be avoided. – In infants, long term continuous topical corticosteroid therapy should be avoided. Adrenal suppression can occur even without occlusion.

– Because of its corticosteroid content avoid long-term treatment with MECOZALEN CORT. Once the inflammatory symptoms have disappeared treatment may be continued with miconazole nitrate 2% cream or powder.

– MECOZALEN CORT can damage certain synthetic materials. Therefore, it is recommended to wear cotton underwear if this clothing comes into contact with the affected area.

– The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may decrease the effectiveness of latex contraceptive agents. Therefore, MECOZALEN CORT should not be used concurrently with a latex condom or latex diaphragm. Visual disturbance 

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

INTERACTION:

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after topical application, clinically relevant interactions are rare. However, in patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored.

Miconazole is a CYP3A4 inhibitor that can decrease the rate of metabolism of hydrocortisone. Serum concentrations of hydrocortisone may be higher with the use of MECOZALEN CORT compared with topical preparations containing hydrocortisone alone. 

PREGNANCY:

Clinical data on the use of MECOZALEN CORT in pregnancy are limited. In animals, corticosteroids are known to cross the placenta and consequently can affect the fetus. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development. The relevance of these findings to humans has not been established.

As a precautionary measure, it is preferable to avoid the use of MECOZALEN CORT during pregnancy. Treatment of large surfaces and the application under occlusive dressing is not recommended.

BREAST-FEEDING

There are no adequate and well-controlled studies on the topical administration of MECOZALEN CORT during breastfeeding. It is not known whether concomitant topical administration of MECOZALEN CORT to the skin could result in sufficient systemic absorption to produce detectable quantities of hydrocortisone and miconazole in breast milk in humans. A risk to the newborn child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from MECOZALEN CORT therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Treatment of large surfaces and the application under occlusive dressing is not recommended.

OVERDOSE:

Adverse Reaction Frequency

Not Known 

Anaphylactic reaction, Hypersensitivity Angioedema, Rash, Contact dermatitis, Erythema, Skin inflammation, Skin hypopigmentation, Application site reaction Vision, blurred Prolonged and excessive use can result in skin irritation, which usually disappears after discontinuation of therapy. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic effects:

Miconazole nitrate is active against dermatophytes and pathogenic yeasts, and many Gram-positive bacteria. Hydrocortisone is an anti-inflammatory steroid. Its anti-inflammatory action is due to reduction in the vascular component of the inflammatory response, suppression of migration of polymorphonuclear leukocytes, and reversal of increased capillary permeability. The vasoconstrictor action of hydrocortisone may also contribute to its anti-inflammatory activity. Pharmacokinetic properties:

Absorption:

Miconazole remains in the skin after topical application for up to 4 days. Systemic absorption of miconazole is limited, with a bioavailability of less than 1% following topical application of miconazole. Plasma concentrations of miconazole and/or its metabolites were measurable 24 and 48 hours after application. Approximately 3% of the dose of hydrocortisone is absorbed after application on the skin.

Distribution:

Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells (10.6%). More than (90%) of hydrocortisone is bound to plasma proteins.

Metabolism and elimination:

The small amount of miconazole that is absorbed is eliminated predominantly in feces as both unchanged drug and metabolites over a four-day post-administration period. Smaller amounts of unchanged drug and metabolites also appear in urine.

The half-life of hydrocortisone is about 100 minutes. Metabolism takes place in the liver and tissues and the metabolites are excreted with the urine, mostly as glucuronides, together with a very small fraction of unchanged hydrocortisone. INCOMPATIBILITIES:

Contact should be avoided between latex products such as contraceptive diaphragms or condoms and MECOZALEN CORT since the constituents of MECOZALEN CORT may damage the latex.

STORAGE CONDITIONS:

“Store at room temperature, below 25 °C”.

“Do not freeze”.

“Keep out of reach of children”.

PRESENTATION:

Aluminium tube contains 15 gram MECOZALEN CORT cream.

Aluminium tube contains 15 gram MECOZALEN CORT ointment.

Miconazole Nitrate 2% + Hydrocortisone (Acetate) 1%

Topical (Cream, Ointment)

COMPOSITION:

Each 100 g of MECOZALEN CORT (cream, ointment) contains: Miconazole nitrate 2g, Hydrocortisone (as Hydrocortisone acetate) 1 g.

EXCIPIENTS:

MECOZALEN CORT cream: Cetylstearyl Alcohol with Ethylene Oxide, Cetostearyl Alcohol, Liquid Paraffin, Benzoic Acid, Disodium Edetate, Butylated Hydroxyanisole, Sodium Hydroxide Solution, Purified Water.

MECOZALEN CORT ointment: Polyethylene, Liquid Paraffin gel.

INDICATIONS:

For the topical treatment of inflamed dermatosis where infection by susceptible organisms and inflammation co-exist, e.g. intertrigo and infected eczema.

Moist or dry eczema or dermatitis including atopic eczema, primary irritant or contact allergic eczema or seborrhoeic eczema including that associated with acne.

Intertriginous eczema including inflammatory intertrigo, perianal and genital dermatitis.

Organisms which are susceptible to miconazole are dermatophytes and pathogenic yeasts (e.g. Candida spp.). Also many Gram- positive bacteria including most strains of Streptococcus and Staphylococcus.

DOSAGE AND ADMINISTRATION:

For topical administration.

Apply MECOZALEN CORT two or three times a day to the affected area, rubbing in gently until it has been absorbed by the skin. Because of its corticosteroid content avoid long-term treatment with MECOZALEN CORT. Once the inflammatory symptoms have disappeared (after about 7 days),

treatment can be continued where necessary with MECOZALEN CORT (miconazole nitrate 2%). Treatment should be continued without interruption until the lesion has completely disappeared (usually after 2 to 5 weeks).

If after about 7 days’ application, no improvement has occurred, cultural isolation of the offending organism should be followed by appropriate local or systemic antimicrobial therapy.

The same dosage applies to both adults and children.

Elderly

Natural thinning of the skin occurs in the elderly, hence corticosteroids should be used sparingly and for short periods of time.

Pediatrics

In infants and children, caution is advised when MECOZALEN CORT is applied to extensive surface areas or under occlusive dressings including baby napkins (diapers). In infants, long term continuous topical corticosteroid therapy should be avoided. CONTRAINDICATIONS:

– True hypersensitivity to miconazole/miconazole nitrate, other imidazole derivatives, hydrocortisone or to any of the excipients. – Tubercular or viral infections of the skin or those caused by Gram-negative bacteria.

WARNINGS AND PRECAUTIONS:

– When MECOZALEN CORT is used by patients taking oral anticoagulants, the anticoagulant effect should be carefully monitored. Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported during treatment with MECOZALEN CORT and with other miconazole topical formulations. If a reaction suggesting hypersensitivity or irritation should occur, the treatment should be discontinued.

– MECOZALEN CORT must not come into contact with the mucosa of the eyes.

– As with any topical corticosteroid, caution is advised with infants and children when MECOZALEN CORT is to be applied to extensive surface areas or under occlusive dressings including baby napkins; similarly, application to the face should be avoided. – In infants, long term continuous topical corticosteroid therapy should be avoided. Adrenal suppression can occur even without occlusion.

– Because of its corticosteroid content avoid long-term treatment with MECOZALEN CORT. Once the inflammatory symptoms have disappeared treatment may be continued with miconazole nitrate 2% cream or powder.

– MECOZALEN CORT can damage certain synthetic materials. Therefore, it is recommended to wear cotton underwear if this clothing comes into contact with the affected area.

– The concurrent use of latex condoms or diaphragms with vaginal anti-infective preparations may decrease the effectiveness of latex contraceptive agents. Therefore, MECOZALEN CORT should not be used concurrently with a latex condom or latex diaphragm. Visual disturbance 

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

INTERACTION:

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited systemic availability after topical application, clinically relevant interactions are rare. However, in patients on oral anticoagulants, such as warfarin, caution should be exercised and anticoagulant effect should be monitored.

Miconazole is a CYP3A4 inhibitor that can decrease the rate of metabolism of hydrocortisone. Serum concentrations of hydrocortisone may be higher with the use of MECOZALEN CORT compared with topical preparations containing hydrocortisone alone. 

PREGNANCY:

Clinical data on the use of MECOZALEN CORT in pregnancy are limited. In animals, corticosteroids are known to cross the placenta and consequently can affect the fetus. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development. The relevance of these findings to humans has not been established.

As a precautionary measure, it is preferable to avoid the use of MECOZALEN CORT during pregnancy. Treatment of large surfaces and the application under occlusive dressing is not recommended.

BREAST-FEEDING

There are no adequate and well-controlled studies on the topical administration of MECOZALEN CORT during breastfeeding. It is not known whether concomitant topical administration of MECOZALEN CORT to the skin could result in sufficient systemic absorption to produce detectable quantities of hydrocortisone and miconazole in breast milk in humans. A risk to the newborn child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from MECOZALEN CORT therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Treatment of large surfaces and the application under occlusive dressing is not recommended.

OVERDOSE:

Adverse Reaction Frequency

Not Known 

Anaphylactic reaction, Hypersensitivity Angioedema, Rash, Contact dermatitis, Erythema, Skin inflammation, Skin hypopigmentation, Application site reaction Vision, blurred Prolonged and excessive use can result in skin irritation, which usually disappears after discontinuation of therapy. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamic effects:

Miconazole nitrate is active against dermatophytes and pathogenic yeasts, and many Gram-positive bacteria. Hydrocortisone is an anti-inflammatory steroid. Its anti-inflammatory action is due to reduction in the vascular component of the inflammatory response, suppression of migration of polymorphonuclear leukocytes, and reversal of increased capillary permeability. The vasoconstrictor action of hydrocortisone may also contribute to its anti-inflammatory activity. Pharmacokinetic properties:

Absorption:

Miconazole remains in the skin after topical application for up to 4 days. Systemic absorption of miconazole is limited, with a bioavailability of less than 1% following topical application of miconazole. Plasma concentrations of miconazole and/or its metabolites were measurable 24 and 48 hours after application. Approximately 3% of the dose of hydrocortisone is absorbed after application on the skin.

Distribution:

Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells (10.6%). More than (90%) of hydrocortisone is bound to plasma proteins.

Metabolism and elimination:

The small amount of miconazole that is absorbed is eliminated predominantly in feces as both unchanged drug and metabolites over a four-day post-administration period. Smaller amounts of unchanged drug and metabolites also appear in urine.

The half-life of hydrocortisone is about 100 minutes. Metabolism takes place in the liver and tissues and the metabolites are excreted with the urine, mostly as glucuronides, together with a very small fraction of unchanged hydrocortisone. INCOMPATIBILITIES:

Contact should be avoided between latex products such as contraceptive diaphragms or condoms and MECOZALEN CORT since the constituents of MECOZALEN CORT may damage the latex.

STORAGE CONDITIONS:

“Store at room temperature, below 25 °C”.

“Do not freeze”.

“Keep out of reach of children”.

PRESENTATION:

Aluminium tube contains 15 gram MECOZALEN CORT cream.

Aluminium tube contains 15 gram MECOZALEN CORT ointment.

CHEMICAL COMPOSITION: Each 1 gr. contains: 20 mg MICONAZOLE NITRATE.

Excipients: Glyceryl Monostearate, Cetostearyl Alcohol, Eumulgin B2, Vaseline, Liquid Paraffin, Glycerin, Methyl Paraben Sodium, Propyl Paraben Sodium, Deionized Water. PHARMACOLOGICAL CLASSIFICATION: Antifungal

MECHANISM OF ACTION:

Miconazole kills fungi and yeasts by interfering with their cell membranes. It works by stopping the fungi from producing a substance called ergosterol, which is an essential component of fungal cell membranes. The disruption in production of ergosterol disrupts the fungal cell membrane, causing holes to appear in it.

The cell membranes of fungi are vital for their survival.

INDICATIONS:

Treatment of most athlete’s foot, jock itch, and ringworm.

Relieves itching, burning, cracking, scaling and discomfort which accompany these conditions. CONTRAINDICATIONS:

In patient has hypersensitivity to the active ingredient or to the excipents.

In patients who never had a vaginal yeast infection diagnosed by a doctor.

SIDE EFFECTS:

Uncommon: Skin irritation (e.g. burning sensation, redness, warmth, itching) at the application site.

Pregnancy and breastfeeding:

• MECOZALEN should be used with caution during pregnancy, and only if the expected benefit to the mother is greater than any possible risk to the developing baby. you should seek medical advice from your doctor before using this medicine if you are pregnant.
• MECOZALEN should be used with caution by breastfeeding mothers, and only if the expected benefit to the mother is greater than any possible risk to the baby. you should seek medical advice from your doctor before using this medicine if you are breastfeeding. If you do use the cream while breastfeeding, you should not apply it to the skin of the breasts shortly before giving a feed, to avoid it being ingested by the nursing infant WARNINGS:

1. Do not use MECOZALEN on children under 2 years of age except under the advice and supervision of a doctor. 2. For external use only.
2. When using MECOZALEN avoid contact with eyes.
3. Stop using MECOZALEN and ask a doctor

• irritation occurs
• there is no improvement within 4 weeks (for athlete’s foot and ringworm) or 2 weeks (for jock itch).

do not use for diaper rash

5. If swallowed, get medical help

DRUG INTERACTIONS:

• Miconazole is unlikely to be absorbed through the skin in sufficient amounts to significantly affect other medicines that you are taking by mouth.
• if you are taking warfarin, there is a very small chance that miconazole absorbed from this cream may enhance the effect of the warfarin.
• If you are using other topical medicines or moisturizers on the same area of skin it is recommended that you leave about 30 minutes between applying each product.

DOSAGE & ADMINISTRATION:

• wash affected area and dry thoroughly

Apply a thin layer over affected area twice daily (morning and night) or as directed by a doctor

• supervise children in the use of this product

 for athlete’s foot, pay special attention to spaces between the toes, wear well-fitting, ventilated shoes and change shoes and socks at least once a day, for athlete’s foot and ringworm use daily for 4 weeks, for jock itch use daily for 2 weeks

• if conditions persist longer, ask a doctor
• This product is not effective on the scalp or nails.

STORAGE:

Store at temperature below 25 °C.

Keep out of reach of children.

PACKAGE:

Aluminum tube contains 15 gr. MECOZALEN cream / carton box.

Aluminum tube contains 30 gr. MECOZALEN cream / carton box.