Mayanmar Product

Eszol Tablets

Eszol Tablets

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:
Vulvovaginal candidosis Pityriasis versicolor
Dermatophytoses caused by organisms susceptible to itraconazole (Trichophyton spp., Microsporum spp., Epidermophyton floccosum) e.g. tinea pedis, tinea cruris, tinea corporis, tinea manuum
Oropharyngeal candidosis
Onychomycosis caused by dermatophytes and/or yeasts The treatment of histoplasmosis
Eszol is indicated in the following systemic fungal conditions when first-line systemic anti-fungal therapy is inappropriate or has proved ineffective. This may be due to underlying pathology, insensitivity of the pathogen or drug toxicity:
 Treatment of aspergillosis and candidosis
 Treatment of cryptococcosis (including cryptococcal meningitis): in immunocompromised patients with cryptococcosis and in all patients with cryptococcosis of the central nervous system.
 Maintenance therapy in AIDS patients to prevent relapse of underlying fungal infection.
Eszol is also indicated in the prevention of fungal infection during prolonged neutropenia when standard therapy is considered inappropriate. It is also indicated in the prevention of fungal infection during prolonged neutropenia when standard therapy is considered inappropriate.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Undesirable effects listed below have been reported in clinical trials with Eszol tablets and/or from spontaneous reports from post-marketing experience for all Eszol formulations. The table below presents adverse drug reactions by System Organ Class. Within each System Organ Class, the adverse drug reactions are presented by incidence, using the following convention:
Very common (> 1/10); Common (> 1/100 to < 1/10); Uncommon (> 1/1,000 to < 1/100); Rare (> /10,000 to < 1/1,000); Very rare (> 1/10,000), Not known (cannot be estimated from the available data).

Adverse Drug Reactions

 

 

 

Infections and infestations

 

 

 

Uncommon

Sinusitis, Upper respiratory tract infection, Rhinitis

 

 

Blood and lymphatic system disorders

 

 

 

Rare

Leukopenia

 

 

Immune system disorders

 

 

 

Uncommon

Hypersensitivity*

 

 

Rare

Serum sickness, Angioneurotic oedema, Anaphylactic reaction

 

 

Metabolism and nutrition disorders

 

 

 

Rare

Hypertriglyceridaemia

 

 

Nervous system disorders

 

 

 

Common

Headache

 

 

Rare

Paraesthesia, Hypoaesthesia, Dysgeusia

 

 

Eye disorders

 

 

 

Rare

Visual disturbance (including diplopia and blurred vision)

 

 

Ear and labyrinth disorder

 

 

 

Rare

Transient or permanent hearing loss*, Tinnitus

 

 

Cardiac disorders

 

 

 

Rare

Congestive heart failure*

 

 

Respiratory, thoracic and mediastinal disorders

 

 

 

Rare

Dyspnoea

 

 

Gastrointestinal disorders

 

 

 

Common

Abdominal pain, Nausea

 

 

Uncommon

Diarrhoea, Vomiting, Constipation, Dyspepsia, Flatulence

 

 

Rare

Pancreatitis

 

 

Hepatobiliary disorders

 

 

 

Uncommon

Hepatic function abnormal

 

 

Rare

Serious hepatotoxicity (including some cases of fatal acute liver failure)*, Hyperbilirubi-

 

naemia

 

 

Skin and subcutaneous tissue disorders

 

 

 

Uncommon

Urticaria, Rash, Pruritus

 

 

Rare

Toxic epidermal necrolysis, Stevens-Johnson syndrome, Acute generalised exanthematous

 

pustulosis, Erythema multiforme, Exfoliative dermatitis, Leukocytoclastic vasculitis,

 

Alopecia, Photosensitivity

 

 

Renal and urinary disorders

 

 

 

Rare

Pollakiuria

 

 

Reproductive system and breast disorders

 

 

 

Uncommon

Menstrual disorder

 

 

Rare

Erectile dysfunction

 

 

General disorders and administration site conditions

 

 

Rare

Oedema

 

 

Investigations

 

 

 

Rare

Blood creatine phosphokinase increased

 

 

What to do if you miss a dose?

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise take it as soon as you remember and then go back to taking it as you would normally.

Things you MUST NOT DO while on this medicine?

CONTRAINDICATIONS
Eszol tablets are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients.
Coadministration of the following drugs is contraindicated with Eszol tablets
CYP3A4 metabolised substrates that can prolong the QT-interval e.g., astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole and terfenadine are contraindicated with Eszol tablets. Coadministration may result in increased plasma concentrations of these substrates which can lead to QTc prolongation and rare occurrences of torsades de pointes.
CYP3A4 metabolised HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin Triazolam and oral midazolam Ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) Eletriptan Nisoldipine
Eszol tablets should not be administered for non-life threatening indications to patients receiving disopyramide or halofantrine.
Eszol tablets should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF except for the treatment of life-threatening or other serious infections.
Eszol tablets must not be used during pregnancy for non life-threatening indications.
Women of childbearing potential taking Eszol tablets should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of Eszol tablets therapy.

What to do if you accidentally take too much (overdose) of the medicine?

OVERDOSE
No data are available.
In the event of overdosage, supportive measures should be employed. Within the first hour after ingestion, gastric lavage may be performed. Activated charcoal may be given if considered appropriate. Itraconazole cannot be removed by haemodialysis. No specific antidote is available.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication. For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store below 30°C.
Keep all medicines out of reach of children

Drug Description

Composition
Each film coated tablet contains:
Itraconazole BP ............ 100 mg
Excipients: Sugar spheres, microcrystalline cellulose, hydroxypropyl methyl cellulose, lactose monohydrate, sodium starch glycolate, croscarmellose sodium, low substituted hydroxypropyl cellulose, povidone K-30, magnesium stearate, colloidal anhydrous silica, opadry II pink 85G54039, purified water, dichloromethane & isopropyl alcohol.
Pharmaceutical Form: Tablets

Indications and dosage.

INDICATIONS
Vulvovaginal candidosis. Pityriasis versicolor
Dermatophytoses caused by organisms susceptible to itraconazole (Trichophyton spp., Microsporum spp., Epidermophyton floccosum) e.g. tinea pedis, tinea cruris, tinea corporis, tinea manuum
Oropharyngeal candidosis
Onychomycosis caused by dermatophytes and/or yeasts The treatment of histoplasmosis
Eszol is indicated in the following systemic fungal conditions when first-line systemic anti-fungal therapy is inappropriate or has proved ineffective. This may be due to underlying pathology, insensitivity of the pathogen or drug toxicity
 Treatment of aspergillosis and candidosis
 Treatment of cryptococcosis (including cryptococcal meningitis): in immunocompromised patients with cryptococcosis and in all patients with cryptococcosis of the central nervous system.
 Maintenance therapy in AIDS patients to prevent relapse of underlying fungal infection.
Eszol is also indicated in the prevention of fungal infection during prolonged neutropenia when standard therapy is considered inappropriate. It is also indicated in the prevention of fungal infection during prolonged neutropenia when standard therapy is considered inappropriate.
DOSAGE AND ADMINISTRATION
Eszol is for oral administration and must be taken immediately after a meal for maximal absorption. Treatment schedules in adults are given below:

Indication

Dose1

Remarks

 

 

 

Vulvovaginal candidosis

200 mg twice daily for 1 day

 

 

 

 

Pityriasis versicolor

200 mg once daily for 7 days

 

 

 

 

Tinea corporis, tinea cruris

100 mg once daily for 15 days or 200 mg

 

 

once daily for 7 days

 

 

 

 

Tinea pedis, tinea manuum

100 mg once daily for 30 days

 

 

 

 

Oropharyngeal candidosis

100 mg once daily for 15 days

Increase dose to 200 mg once daily for 15 days

 

 

in AIDS or neutropenic patients because of im-

 

 

paired absorption in these groups.

 

 

 

Onychomycosis (toenails with or without

200 mg once daily for 3 months

 

fingernail involvement)

 

 

 

 

 

For skin, vulvovaginal and oropharyngeal infections, optimal clinical and mycological effects are reached 1 - 4 weeks after cessation of treatment and for nail infections, 6 - 9 months after the cessation of treatment. This is because elimination of itraconazole from skin, nails and mucous membranes is slower than from plasma.
The length of treatment for systemic fungal infections should be dictated by the mycological and clinical response to therapy

Indication

Dose1

Remarks

 

 

 

Aspergillosis

200 mg once daily

Increase dose to 200 mg twice daily in case of

 

 

invasive or disseminated disease

 

 

 

Candidosis

100-200 mg once daily

Increase dose to 200 mg twice daily in case

 

 

of invasive or disseminated disease

 

 

 

Non-meningeal Cryptococcosis

200 mg once daily

 

 

 

 

Cryptococcal meningitis

 

See Special Warnings and Precautions for use

 

 

 

Histoplasmosis

200 mg once daily- 200 mg twice daily

 

 

 

 

Maintenance in AIDS

200 mg twice daily

See note on impaired absorption below

 

 

 

Prophylaxis in neutropenia

200 mg once daily

See note on impaired absorption below

 

 

 

The duration of treatment should be adjusted depending on the clinical response.
Impaired absorption in AIDS and neutropenic patients may lead to low itraconazole blood levels and lack of efficacy. In such cases, blood level monitoring and if necessary, an increase in itraconazole dose to 200 mg twice daily, is indicated
Use in children
Not recommended. See Special Warnings and Precautions for use.
In Elderly
Not recommended. See Special Warnings and Precautions for use.
Use in patients with renal impairment
The oral bioavailability of itraconazole may be lower in patients with renal insufficiency, a dose adjustment may be considered. See Special Warnings and Precautions for use.
Use in patients with hepatic impairment
Itraconazole is predominantly metabolised by the liver. The terminal half-life of itraconazole in cirrhotic patients is somewhat prolonged. The oral bioavailability in cirrhotic patients is somewhat decreased. A dose adjustment may be considered. See Special Warnings and Precautions for use.

Side effects and drug interactions.

ADVERSE EFFECTS
Undesirable effects listed below have been reported in clinical trials with Eszol tablets and/or from spontaneous reports from post-marketing experience for all Eszol formulations. The table below presents adverse drug reactions by System Organ Class. Within each System Organ Class, the adverse drug reactions are presented by incidence, using the following convention:
Very common (> 1/10); Common (> 1/100 to < 1/10); Uncommon (> 1/1,000 to < 1/100); Rare (> /10,000 to < 1/1,000); Very rare (> 1/10,000), Not known (cannot be estimated from the available data).

Adverse Drug Reactions

 

 

 

Infections and infestations

 

 

 

Uncommon

Sinusitis, Upper respiratory tract infection, Rhinitis

 

 

Blood and lymphatic system disorders

 

 

 

Rare

Leukopenia

 

 

Immune system disorders

 

 

 

Uncommon

Hypersensitivity*

 

 

Rare

Serum sickness, Angioneurotic oedema, Anaphylactic reaction

 

 

Metabolism and nutrition disorders

 

 

 

Rare

Hypertriglyceridaemia

 

 

Nervous system disorders

 

 

 

Common

Headache

 

 

Rare

Paraesthesia, Hypoaesthesia, Dysgeusia

 

 

Eye disorders

 

 

 

Rare

Visual disturbance (including diplopia and blurred vision)

 

 

Ear and labyrinth disorder

 

 

 

Rare

Transient or permanent hearing loss*, Tinnitus

 

 

Cardiac disorders

 

 

 

Rare

Congestive heart failure*

 

 

Respiratory, thoracic and mediastinal disorders

 

 

 

Rare

Dyspnoea

 

 

Gastrointestinal disorders

 

 

 

Common

Abdominal pain, Nausea

 

 

Uncommon

Diarrhoea, Vomiting, Constipation, Dyspepsia, Flatulence

 

 

Rare

Pancreatitis

 

 

Hepatobiliary disorders

 

 

 

Uncommon

Hepatic function abnormal

 

 

Rare

Serious hepatotoxicity (including some cases of fatal acute liver failure)*, Hyperbilirubi-

 

naemia

 

 

Skin and subcutaneous tissue disorders

 

 

 

Uncommon

Urticaria, Rash, Pruritus

 

 

Rare

Toxic epidermal necrolysis, Stevens-Johnson syndrome, Acute generalised exanthematous

 

pustulosis, Erythema multiforme, Exfoliative dermatitis, Leukocytoclastic vasculitis,

 

Alopecia, Photosensitivity

 

 

Renal and urinary disorders

 

 

 

Rare

Pollakiuria

 

 

Reproductive system and breast disorders

 

 

 

Uncommon

Menstrual disorder

 

 

Rare

Erectile dysfunction

 

 

General disorders and administration site conditions

 

 

Rare

Oedema

 

 

Investigations

 

 

 

Rare

Blood creatine phosphokinase increased

 

 

*See Special Warnings and Precautions for use
INTERACTIONS WITH OTHER MEDICINAL PRODUCTS
Drugs affecting the absorption of itraconazole
Drugs that reduce the gastric acidity impair the absorption of itraconazole from Eszol tablets.
Drugs affecting the metabolism of itraconazole
Itraconazole is mainly metabolised through the cytochrome CYP3A4. Interaction studies have been performed with rifampicin, rifabutin and phenytoin, which are potent inducers of CYP3A4. Since the bioavailability of itraconazole and hydroxy-itraconazole was decreased in these studies to such an extent that efficacy may be largely reduced, the combination of itraconazole with these potent enzyme inducers is not recommended. No formal study data are available for other enzyme inducers, such as carbamazepine, Hypericum perforatum |(St John's Wort), phenobarbital and isoniazid, but similar effects should be anticipated.
Potent inhibitors of this enzyme such as ritonavir, indinavir, clarithromycin and erythromycin may increase the bioavailability of itraconazole.
Effects of itraconazole on the metabolism of other drugs
Itraconazole can inhibit the metabolism of drugs metabolised by the cytochrome 3A family. This can result in an increase and/or a prolongation of their effects, including side effects. When using concomitant medication, the corresponding label should be consulted for information on the route of administration. After stopping treatment, itraconazole plasma concentrations decline gradually, depending on the dose and duration of treatment. This should be taken into account when the inhibitory effect of itraconazole on co-administered drugs is considered.
Examples are:
The following drugs are contraindicated with itraconazole:
Astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole or terfenadine are contraindicated with Eszol since co-administration may result in increased plasma concentrations of these substrates, which can lead to QT prolongation and rare occurrences of torsades de pointes.
CYP3A4 metabolised HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin Triazolam and oral midazolam Ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) Eletriptan Nisoldipine
Caution should be exercised when co-administering itraconazole with calcium channel blockers due to an increased risk of congestive heart failure. In addition to possible pharmacokinetic interactions involving the drug metabolising enzyme CYP3A4, calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole.
The following drugs should be used with caution, and their plasma concentrations, effects or side effects should be monitored. Their dosage, if co-administered with itraconazole, should be reduced if necessary:
Oral anticoagulants HIV protease inhibitors such as ritonavir, indinavir, saquinavir
Certain antineoplastic agents such as vinca alkaloids, busulfan, docetaxel and trimetrexate CYP3A4 metabolised calcium channel blockers such as dihydropyridines and verapamil
Certain immunosuppressive agents:
ciclosporin, tacrolimus and rapamycin (also known as sirolimus) Certain glucocorticoids such as budesonide, dexamethasone, fluticasone and methyl prednisolone Digoxin (via inhibition of P-glycoprotein)
Others:
carbamazepine, cilostazol, buspirone, disopyramide, alfentanil, alprazolam, brotizolam, midazolam IV, rifabutin, ebastine, fentanyl, halofantrine, repaglinide and reboxetine. The importance of the concentration increase and the clinical relevance of these changes during co-administration with itraconazole remain to be established.
No interaction of itraconazole with zidovudine (AZT) and fluvastatin has been observed.
No inducing effects of itraconazole on the metabolism of ethinyloestradiol and norethisterone were observed.
Effect on protein binding
In vitro studies have shown that there are no interactions on the plasma protein binding between itraconazole and imipramine, propranolol, diazepam, cimetidine, indometacin, tolbutamide or sulfamethazine.
ADVERSE DRUG REACTION
"Inform doctors about unexpected reactions after using drugs."

Warnings and precautions

SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Cross-hypersensitivity
There is no information regarding cross hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used in prescribing Eszol tablets to patients with hypersensitivity to other azoles.
Cardiac effects
Itraconazole has been shown to have a negative inotropic effect and Eszol tablets have been associated with reports of congestive heart failure. Heart failure was more frequently reported among spontaneous reports of 400 mg total daily dose than among those of lower total daily doses, suggesting that the risk of heart failure might increase with the total daily dose of itraconazole.
Eszol should not be used in patients with congestive heart failure or with a history of congestive heart failure unless the benefit clearly outweighs the risk. This individual benefit/risk assessment should take into consideration factors such as the severity of the indication, the dose and duration of treatment (e.g. total daily dose), and individual risk factors for congestive heart failure. These risk factors include cardiac disease, such as ischemic and valvular disease; significant pulmonary disease, such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders. Such patients should be informed of the signs and symptoms of congestive heart failure, should be treated with caution, and should be monitored for signs and symptoms of congestive heart failure during treatment; if such signs or symptoms do occur during treatment, Eszol should be discontinued.
Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers. Therefore, caution should be exercised when co-administering itraconazole and calcium channel to an increased risk of congestive heart failure.
Hepatic effects
Very rare cases of serious hepatotoxicity, including some cases of fatal acute liver failure, have occurred with the use of Eszol tablets. Most of these cases involved patients who, had pre-existing liver disease, were treated for systemic indications, had significant other medical conditions and/or were taking other hepatotoxic drugs. Some patients had no obvious risk factors for liver disease. Some of these cases were observed within the first month of treatment, including some within the first week. Liver function monitoring should be considered in patients receiving Eszol tablets treatment. Patients should be instructed to promptly report to their physician signs and symptoms suggestive of hepatitis such as anorexia, nausea, vomiting, fatigue, abdominal pain or dark urine. In these patients treatment should be stopped immediately and liver function testing should be conducted.
In patients with raised liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment should not be started unless the expected benefit exceeds the risk of hepatic injury. In such cases liver enzyme monitoring is necessary.
Reduced gastric acidity
Absorption of itraconazole from Eszol tablets is impaired when gastric acidity is reduced. In patients also receiving acid neutralising medicines (e.g. aluminium hydroxide), these should be administered at least 2 hours after the intake of Eszol tablets. In patients with achlorhydria, such as certain AIDS patients and patients on acid secretion suppressors (e.g. H2 -antagonists, proton-pump inhibitors), it is advisable to administer Eszol tablets with a cola beverage.
Use in children
Clinical data on the use of Eszol tablets in paediatric patients is limited. Eszol tablets should not be used in paediatric patients unless the potential benefit outweighs the potential risks.
Use in elderly
Clinical data on the use of Eszol tablets in elderly patients is limited. Eszol tablets should not be used in these patients unless the potential benefit outweighs the potential risks. In general, it is recommended that the dose selection for an elderly patient should be taken into consideration, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Hepatic impairment
Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when the drug is administered in this patient population.
Renal impairment
Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when this drug is administered in this patient population. The oral bioavailability of itraconazole may be lower in patients with renal insufficiency. Dose adaptation may be considered.
Hearing Loss
Transient or permanent hearing loss has been reported in patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated. The hearing loss usually resolves when treatment is stopped, but can persist in some patients.
Immunocompromised patients
In some immunocompromised patients (e.g., neutropenic, AIDS or organ transplant patients), the oral bioavailability of Eszol tablets may be decreased.
Patients with immediately life-threatening systemic fungal infections
Due to the pharmacokinetic properties, Eszol tablets are not recommended for initiation of treatment in patients with immediately life-threatening systemic fungal infections.
Patients with AIDS
In patients with AIDS having received treatment for a systemic fungal infection such as sporotrichosis, blastomycosis, histoplasmosis or cryptococcosis (meningeal or non-meningeal) and who are considered at risk for relapse, the treating physician should evaluate the need for a maintenance treatment.
Neuropathy
If neuropathy occurs which may be attributable to Eszol tablets, the treatment should be discontinued.
Disorders of Carbohydrate Metabolism
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Cross-resistance
In systemic candidosis, if fluconazole-resistant strains of Candida species are suspected, it cannot be assumed that these are sensitive to itraconazole, hence their sensitivity should be tested before the start of Eszol therapy.
Interaction Potential
Eszol has a potential for clinically important drug interactions. Itraconazole should not be used within 2 weeks after discontinuation of treatment with CYP 3A4 inducing agents (rifampicin, rifabutin, phenobarbital, phenytoin, carbamazepine, Hypericum perforatum (St. John´s wort). The use of itraconazole with these drugs may lead to subtherapeutic plasma levels of itraconazole and thus treatment failure.
PREGNANCY AND LACTATION
Pregnancy
Eszol tablets must not be used during pregnancy except for life-threatening cases where the potential benefit to the mother outweighs the potential harm to the foetus. In animal studies itraconazole has shown reproduction toxicity.
There is limited information on the use of Eszol during pregnancy. During post-marketing experience, cases of congenital abnormalities have been reported. These cases included skeletal, genitourinary tract, cardiovascular and ophthalmic malformations as well as chromosomal and multiple malformations. A causal relationship with Eszol has not been established.
Epidemiological data on exposure to Eszol during the first trimester of pregnancy-mostly in patients receiving short-term treatment f or vulvovaginal candidosis-did not show an increased risk for malformations as compared to control subjects not exposed to any known teratogens.
Women of child bearing potential
Women of childbearing potential taking Eszol tablets should use contraceptive precautions. Effective contraception should be continued until the next menstrual period following the end of Eszol therapy.
Lactation
A very small amount of itraconazole is excreted in human milk. The expected benefits of Eszol therapy should be weighed against the risks of breast feeding. In case of doubt, the patient should not breast feed.

Overdosage and Contraindications

OVERDOSE
No data are available.
In the event of overdosage, supportive measures should be employed. Within the first hour after ingestion, gastric lavage may be performed. Activated charcoal may be given if considered appropriate. Itraconazole cannot be removed by haemodialysis. No specific antidote is available.
CONTRAINDICATIONS
Eszol tablets are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients.
Coadministration of the following drugs is contraindicated with Eszol tablets
CYP3A4 metabolised substrates that can prolong the QT-interval e.g., astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole and terfenadine are contraindicated with Eszol tablets. Coadministration may result in increased plasma concentrations of these substrates which can lead to QTc prolongation and rare occurrences of torsades de pointes.
CYP3A4 metabolised HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin Triazolam and oral midazolam Ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) Eletriptan Nisoldipine
Eszol tablets should not be administered for non-life threatening indications to patients receiving disopyramide or halofantrine.
Eszol tablets should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF except for the treatment of life-threatening or other serious infections.
Eszol tablets must not be used during pregnancy for non life-threatening indications.
Women of childbearing potential taking Eszol tablets should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of Eszol tablets therapy.

Clinical pharmacology.

Pharmacotherapeutic Group: Antifungal
ATC code: J02A C02
PHARMACOLOGICAL PROPERTIES Itraconazole, a triazole derivative, has a broad spectrum of activity.
In vitro studies have demonstrated that itraconazole impairs the synthesis of ergosterol in fungal cells. Ergosterol is a vital cell membrane component in fungi. Impairment of its synthesis ultimately results in an antifungal effect.
For itraconazole, breakpoints have only been established for Candida spp. from superficial mycotic infections (CLSI M27-A2, breakpoints have not been established for EUCAST methodology). The CLSI breakpoints are as follows: susceptible < 0.125; susceptible, dose-dependent 0.25-0.5 and resistant > 1μg/mL. Interpretive breakpoints have not been established for the filamentous fungi.
In vitro studies demonstrate that itraconazole inhibits the growth of a broad range of fungi pathogenic for humans at concentrations usually < 1 µg/ml. These include: dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeasts (Candida spp., including C. albicans, C. glabrata and C. krusei, Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp.); Aspergillus spp.; Histoplasma spp.;
Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsecaea spp.; Cladosporium spp.; Blastomyces dermatitidis; Coccidiodes immitis; Pseudallescheria boydii; Penicillium marneffei; and various other yeasts and fungi.
Candida krusei, Candida glabrata and Candida tropicalis are generally the least susceptible Candida species, with some isolates showing unequivocal resistance to itraconazole in vitro.
The principal fungus types that are not inhibited by itraconazole are Zygomycetes (e.g. Rhizopus spp., Rhizomucor spp., Mucor spp. and Absidia spp.), Fusarium spp., Scedosporium proliferans and Scopulariopsis spp.
Azole resistance appears to develop slowly and is often the result of several genetic mutations. Mechanisms that have been described are overexpression of ERG11, which encodes the target enzyme 14α-demethylase, point mutations in ERG11 that lead to decreased target affinity and/or transporter overexpression resulting in increased efflux. Cross resistance between members of the azole class has been observed within Candida spp., although resistance to one member of the class does not necessarily confer resistance to other azoles. Itraconazole-resistant strains of Aspergillus fumigatus have been reported.
Pharmacokinetic Properties:
The pharmacokinetics of itraconazole has been investigated in healthy subjects, special populations and patients after single and multiple dosing.
Absorption
Itraconazole is rapidly absorbed after oral administration. Peak plasma concentrations of the unchanged drug are reached within 2 to 5 hours following an oral dose. The observed absolute bioavailability of itraconazole is about 55%. Oral bioavailability is maximal when the tablets are taken immediately after a full meal.
Distribution
Most of the itraconazole in plasma is bound to protein (99.8%) with albumin being the main binding component (99.6% for the hydroxy- metabolite). It has also a marked affinity for lipids. Only 0.2% of the itraconazole in plasma is present as free drug. Itraconazole is distributed in a large apparent volume in the body (> 700 L), suggesting its extensive distribution into tissues: Concentrations in lung, kidney, liver, bone, stomach, spleen and muscle were found to be two to three times higher than corresponding concentrations in plasma. Brain to plasma ratios were about 1 as measured in beagle dogs. The uptake into keratinous tissues, skin in particular, is up to four times higher than in plasma.
Metabolism
Itraconazole is extensively metabolised by the liver into a large number of metabolites. One of the main metabolites is hydroxy-itraconazole, which has in vitro antifungal activity comparable to itraconazole. Plasma concentrations of the hydroxy-itraconazole are about twice those of itraconazole.
As shown in in vitro studies, CYP 3A4 is the major enzyme that is involved in the metabolism of itraconazole.
Elimination
Itraconazole is excreted as inactive metabolites to about 35% in urine within one week and to about 54% with faeces. Renal excretion of the parent drug accounts for less than 0.03% of the dose, whereas fecal excretion of unchanged drug varies between 3 – 18% of the dose. Itraconazole clearance decreases at higher doses due to saturable hepatic metabolism.
Linearity/non-linearity
As a consequence of non-linear pharmacokinetics, itraconazole accumulates in plasma during multiple dosing. Steady-state concentrations are generally reached within about 15 days, with Cmax and AUC values 4 to 7-fold higher than those seen after a single dose. The mean elimination half-life of itraconazole is about 40 hours after repeated dosing.
Special Populations
Hepatic Insufficiency: A pharmacokinetic study using a single 100 mg dose of itraconazole (one 100 mg tablet) was conducted in 6 healthy and 12 cirrhotic subjects. No statistically significant differences in AUC were seen between these two groups. A statistically significant reduction in average Cmax (47%) and a two fold increase in the elimination half-life (37 ± 17 versus 16 ±5 hours) of itraconazole were noted in cirrhotic subjects compared with healthy subjects.
Data are not available in cirrhotic patients during long-term use of itraconazole.
Renal Insufficiency:
Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when the drug is administered in this patient population.
STORAGE CONDITION
Store below 30°C.
Keep all medicines out of reach of children
SHELF-LIFE
24 months
DOSAGE FORMS AND PACKAGING AVAILABLE
Alu-Alu blister of 10 tablets, 1 or 3 blisters are in a carton.
NAME AND ADDRESS OF MANUFACTURER
Kusum Healthcare Pvt. Ltd. SP 289(A), RIICO Indl. Area,
Chopanki, Bhiwadi (Rajasthan), India
MM Reg. No.: 1812AA 7080

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare
D-158A, OKHLA,INDUSTRIAL AREA,
PHASE-I, NEW DELHI,
Pin 110020
INDIA
Tel: 011-41005147, 011-40514919
Fax: +91-11-40527575