CANDIFORCE-200: Composition, Description, Pharmacological Action, Precaution, Adverse Effects, Dosage, Storage, Uses
CANDIFORCE - 200
Itraconazole Capsules BP
______________________________________
COMPOSITION :
Each HPMC capsule contains
Itraconazole BP 200 mg
Excipients q.s.
Approved colors used in the capsule shells. (Carmoisine, Ponceau-4R & Titanium Dioxide IP)
DESCRIPTION:
Itraconazole is a synthetic triazole antifungal agent. Itraconazole is indicated for the treatment of the fungal infections in immunocompromised and non-immunocompromised patients.
PHARMACOLOGICAL ACTION:
1.PHARMACODYNAMIC / MECHANISM OF ACTION :
In vitro studies have demonstrated that itraconazole inhibits the cytochrome P450-dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.
2.PHARMACOKINETICS :
A.ABSORPTION & PLASMA LEVELS -
Itraconazole is absorbed from the gastrointestinal tract when given orally either as capsules containing itraconazole.
Absorption from the capsule formulation is enhanced by an acidic gastric environment and is greatest when doses are taken with food.
Peak plasma concentrations are achieved between 1.5 and 5 hours after a dose of the capsule, and a steady-state is reached within 15 days during daily dosing. Peak plasma concentrations at steady state of about 2 micrograms/ml have been reported after daily doses of 200 mg.
Bioavailability increases with the dose of 100 to 400 mg in such a manner as to suggest that itraconazole undergoes saturable metabolism. Itraconazole is highly protein-bound; only 0.2% circulates as a free drug. The plasma protein binding of itraconazole is 99.8% and that of hydroxyitraconazole is 99.5%.
B.DISTRIBUTION -
Itraconazole is widely distributed but only small amounts diffuse into the CSF. Concentrations attained in the skin, sebum, pus, and many organs and tissues are several times higher than simultaneous plasma concentrations.
Therapeutic concentrations of itraconazole remain in the skin and mucous membranes for 1 to 4 weeks after the drug is stopped. Small amounts are distributed into breast milk.
C.METABOLISM -
Itraconazole is metabolized in the liver mainly by cytochrome P450 isoenzyme CYP3A4. The major metabolite, hydroxyitraconazole, has antifungal activity comparable with that of itraconazole.
D.EXCRETION -
Itraconazole is also excreted as inactive metabolites in the bile or urine; 3 to 18% is excreted in the feces as unchanged drug. Small amounts are eliminated in the stratum corneum and hair. Itraconazole is not removed by dialysis.
CONTRAINDICATIONS :
Itraconazole capsules should be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
PRECAUTIONS / WARNINGS :
Itraconazole capsules should be administered after a full meal. Under fasted conditions, itraconazole absorption was decreased in the presence of decreased gastric acidity. The absorption of itraconazole may be decreased with the concomitant administration of antacid or gastric acid secretion suppressors. Studies conducted under fasted conditions demonstrated that administration with 8 ounces of a cola beverage resulted in increased absorption of itraconazole in AIDS patients with relative or absolute achlorhydria. This increase relative to the effects of a full meal is unknown.
(a) HEPATIC EFFECTS -
Itraconazole capsules have been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-exciting liver disease nor or serious underlying medical condition, and some of these cases developed within the first week of treatment. If clinical signs or symptoms develop that are consistent with liver disease, treatment should be discontinued and liver function testing performed. Continued Itraconazole capsules use or reinstitution of treatment with itraconazole capsules is strongly discouraged unless there is a serious or life-threatening situation where the expected benefit exceeds the risk.
(b) CARDIAC DYSRHYTHMIAS -
Life-threatening cardiac dysrhythmias and/or sudden death have
occurred in patients using cisapride, pimozide, levacetylmethadol (levomethadyl), or quinidine concomitantly with itraconazole capsules and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with Itraconazole is contraindicated.
(c) CARDIAC DISEASE :
Itraconazole Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
Itraconazole capsules should not be used for other indications in patients with evidence of ventricular dysfunction unless the benefit clearly outweighs the risk.
For patients with risk factors for congestive heart failure, physicians should carefully review the risk and benefits of Itraconazole capsules therapy. These risk factor factors cardiac diseases 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 CHF, should be treated with caution, and should be monitored for signs and symptoms of CHF during treatment. If signs or symptoms of CHF appear during administration of itraconazole capsules, discontinue administration.
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 used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHF. Concomitant administration of itraconazole capsules and nisoldipine is contraindicated.
Cases of CHF, peripheral edema, and pulmonary edema have been reported in the post-marketing period among patients being treated for onychomycosis and/or systemic fungal infections.
(d) PREGNANCY/LACTATION
There are no studies in pregnant women. Itraconazole capsules should be used for the treatment of systemic fungal infections in pregnancy only if the benefit outweighs the potential risk.
Itraconazole capsules should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. Itraconazole capsules should not be administered to women of childbearing potential for the treatment of onychomycosis unless they are using effective measures to prevent pregnancy and they begin therapy on the second or third day following the onset of menses. Effective contraception should be continued throughout itraconazole capsules therapy and for 2 months following the end of treatment.
(e) CHILDREN
Itraconazole capsule is safe and effective in most fungal organisms causing superficial infection.
(f) LIVER
Inform your doctor or pharmacist if you develop signs of jaundice like yellowing of eyes & skin itching & clay colored stools while taking this medicine.
(g) ALCOHOL
Do not consume alcohol with itraconazole.
Itraconazole is a triazole antifungal given orally for the treatment of oropharyngeal and vulvovaginal candidiasis, for pityriasis Versicolor, for dermatophytosis unresponsive to topical treatment, for onychomycosis, and for systemic infections Including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis. It is also given for the prophylaxis of fungal infections in immunocompromised patients.
Itraconazole capsules are also indicated for the treatment of the following fungal infections in the non-immunocompromised patient:
1. Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguis), and
2. Onychomycosis of the fingernail due to dermatophytes (tinea unguium).
occurred in patients using cisapride, pimozide, levacetylmethadol (levomethadyl), or quinidine concomitantly with itraconazole capsules and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with Itraconazole is contraindicated.
(c) CARDIAC DISEASE :
Itraconazole Capsules should not be administered for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
Itraconazole capsules should not be used for other indications in patients with evidence of ventricular dysfunction unless the benefit clearly outweighs the risk.
For patients with risk factors for congestive heart failure, physicians should carefully review the risk and benefits of Itraconazole capsules therapy. These risk factor factors cardiac diseases 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 CHF, should be treated with caution, and should be monitored for signs and symptoms of CHF during treatment. If signs or symptoms of CHF appear during administration of itraconazole capsules, discontinue administration.
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 used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHF. Concomitant administration of itraconazole capsules and nisoldipine is contraindicated.
Cases of CHF, peripheral edema, and pulmonary edema have been reported in the post-marketing period among patients being treated for onychomycosis and/or systemic fungal infections.
(d) PREGNANCY/LACTATION
There are no studies in pregnant women. Itraconazole capsules should be used for the treatment of systemic fungal infections in pregnancy only if the benefit outweighs the potential risk.
Itraconazole capsules should not be administered for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy. Itraconazole capsules should not be administered to women of childbearing potential for the treatment of onychomycosis unless they are using effective measures to prevent pregnancy and they begin therapy on the second or third day following the onset of menses. Effective contraception should be continued throughout itraconazole capsules therapy and for 2 months following the end of treatment.
(e) CHILDREN
Itraconazole capsule is safe and effective in most fungal organisms causing superficial infection.
(f) LIVER
Inform your doctor or pharmacist if you develop signs of jaundice like yellowing of eyes & skin itching & clay colored stools while taking this medicine.
(g) ALCOHOL
Do not consume alcohol with itraconazole.
THERAPEUTIC INDICATIONS & USAGE :
Itraconazole is a triazole antifungal given orally for the treatment of oropharyngeal and vulvovaginal candidiasis, for pityriasis Versicolor, for dermatophytosis unresponsive to topical treatment, for onychomycosis, and for systemic infections Including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, paracoccidioidomycosis, and sporotrichosis. It is also given for the prophylaxis of fungal infections in immunocompromised patients.
Itraconazole capsules are also indicated for the treatment of the following fungal infections in the non-immunocompromised patient:
1. Onychomycosis of the toenail, with or without fingernail involvement, due to dermatophytes (tinea unguis), and
2. Onychomycosis of the fingernail due to dermatophytes (tinea unguium).
DOSAGE, ADMINISTRATION, & USES:
1.TREATMENT OF OROPHARYNGEAL CANDIDIASIS;
The dose is 200mg of 1 capsule with AIDS or neutropenia daily for 15days.
2.TREATMENT OF VULVOVAGINAL CANDIDIASIS;
The dose is 200mg of 1 capsule twice daily for 1day.
3.TREATMENT OF PTYRIASIS VERSICOLOR;
The dose is 200mg 1 capsule daily for 7 days.
4. TREATMENT OF ONYCHOMYCOSIS;
The dose is 200mg 1capsule daily for 3 months or pulse therapy with 200mg twice daily for 7days repeated once or twice after drug-free intervals of 21days.
5.TREATMENT OF DERMATOPHYTOSIS
The dose is 200mg 1 capsule daily for 7days.
6.TREATMENT OF TINEACORPORIS
AND TINEACRURIS;
The dose is 200mg 1 capsule daily for 7days.
7.TREATMENT OF TINEAPEDIS / TINEAMANUUM;
The dose is 200mg 1capsule daily for 7 days.
8. TREATMENT OF BLASTOMYCOSIS
AND HISTOPLASMOSIS;
The recommended dose is 200 mg of itraconazole one capsule once daily. If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses.
9.TREATMENT OF ASPERGILLOSIS;
A daily dose of 200 to 400 mg (1-2 capsules) of itraconazole is recommended.
10. TREATMENT IN LIFE-THREATENING SITUATIONS ;
A loading dose of 200 mg of itraconazole three times daily for 3 days has been given. A dose of 200 mg daily is used for primary or secondary prophylaxis.
11. TREATMENT OF SYSTEMIC INFECTIONS;
For systemic infections, itraconazole is given in usual doses of 100 to 200 mg once daily, increased to 200 mg twice daily for invasive or disseminated infections, including cryptococcal meningitis.
12. ADMINISTRATION IN CHILDREN ;
For Dermatophyte infections :
. 12 to 18 years of age, 200 mg daily for 7 days (pityversicoloricolour); 200 mg twice daily for 7 days (tinea pedis and tinea manuum).
For onychomycosis :
. 12 to 18 years, either 200 mg daily for 3 months, or courses of 200 mg twice daily for 7 days, repeated after intervals of 21 days to a total of 2 courses for infections of the fingernails and 3 courses for toenail infections.
RENAL FAILURE:
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.
ELDERLY:
Transient or permanent hearing loss has been reported in elderly patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated. Itraconazole should be used with care in elderly patients.
The recommended dose is 200 mg of itraconazole one capsule once daily. If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses.
9.TREATMENT OF ASPERGILLOSIS;
A daily dose of 200 to 400 mg (1-2 capsules) of itraconazole is recommended.
10. TREATMENT IN LIFE-THREATENING SITUATIONS ;
A loading dose of 200 mg of itraconazole three times daily for 3 days has been given. A dose of 200 mg daily is used for primary or secondary prophylaxis.
11. TREATMENT OF SYSTEMIC INFECTIONS;
For systemic infections, itraconazole is given in usual doses of 100 to 200 mg once daily, increased to 200 mg twice daily for invasive or disseminated infections, including cryptococcal meningitis.
12. ADMINISTRATION IN CHILDREN ;
For Dermatophyte infections :
. 12 to 18 years of age, 200 mg daily for 7 days (pityversicoloricolour); 200 mg twice daily for 7 days (tinea pedis and tinea manuum).
For onychomycosis :
. 12 to 18 years, either 200 mg daily for 3 months, or courses of 200 mg twice daily for 7 days, repeated after intervals of 21 days to a total of 2 courses for infections of the fingernails and 3 courses for toenail infections.
RENAL FAILURE:
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.
ELDERLY:
Transient or permanent hearing loss has been reported in elderly patients receiving treatment with itraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated. Itraconazole should be used with care in elderly patients.
ADVERSE / SIDE EFFECTS:
The most common adverse effects are;
(a) Dyspepsia
(b) Abdominal pain
(c) Nausea
(d) Vomiting
(e) Constipation
(f) Diarrhea
(g) Headache
(h) Dizziness
(I) Allergic
(b) Abdominal pain
(g) Headache
(I) Allergic
An isolated case of Stevens-Johnson syndrome.
Live
An increase in liver enzyme values has occurred in some patients and the case of hepatitis and cholestatic jaundice, especially those treated for more than one month.
Heart
Heart failure and pulmonary edema have been reported.
OVERDOSAGE:
Itraconazole is not removed by dialysis. In the event of accidental overdose, supportive measures, including gastric lavage with sodium bicarbonate, should be employed.
STORAGE:
Stored in a dry place at a temperature, not exceed 30-degree Celsius. Protect from light. keep out of reach of children.
Manufactured by ;
Mankind Pharma Ltd.
Comments
Post a Comment