COMPOSITION :
Itraconazole Capsule 100 mg, each capsule contains : Itraconazole pellets equivalent to Itraconazole 100 mg.
DESCRIPTIONS :
Itraconazole with Itraconazole pellets (equivalent to Itraconazole) as active ingredient is available in Capsule 100 mg.
INDICATIONS :
Itraconazole is indicated for treatment of :
- Gynaecological : Vulvovaginal candidacies.
- Dermatological/Opthalmological :
- Pityriasis versicolor, dermatomycosis, fungal keratitis and oral candidacies.
- Onychomycosis caused by dermatofit and/or yeast.
- Systemic mycosis : Systemic aspergillosis and candidacies, cryptoccosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic tropic mycosis.
DOSAGE AND ADMINISTRATIONS :
Taking immediately after a full meal is essential to ensure optimal absorption. Capsules must be swallowed whole.
- Blastomycosis = 100 mg once daily until 200 mg twice a day during 6 months.
- Gynaecological : Vulvovaginal candidacies = 200 mg twice a day during one day or 200 mg once a day during 3 days.
- Dermatological/Opthalmological :
- Pityriasis versicolor = 200 mg once day during a week.
- Dermatomycosis = 200 mg once a day or 100 mg once a day during 7 days or 15 days.
- Area with highly keratinisation such as tinea pedis and tinea manus need the dose about 200 mg twice a day during 7 days or 100 mg per day during 30 days.
- Oral candidacies = 100 mg once a day during 15 days.
- Some patients with immunocompromized such as neutropenia, AIDS or organ transplanted patient have lower level of oral bioavailability. Therefore, the dose should be given 2 times higher than usual.
- Fungal keratitis = 200 mg once a day during 21 days.
- Other systemic mycoses :
| Other Systemic Mycoses Dose and Duration of Therapy | ||||
| Indication | Dose | Median duration | ||
| Aspergillosis
|
200 mg once daily | 2 – 5 months
If the case is invasive or disseminated, the dose should be increased twice daily. |
||
| Non-meningeal Cryptocosis | 200 mg once daily | 2 months – 1 year
Supported treatment (meningeal case) 200 mg once daily. |
||
| Cryptococcal meningitis | 200 mg twice daily | |||
| Histoplasmosis | 200 mg once daily or 200 mg twice daily | 8 months | ||
| Sporotrichosis | 100 mg once daily | 3 months | ||
| Paracoccidioidomycosis | 100 mg once daily | 6 months | ||
| Blastomycosis | 100 mg once a day 200 mg twice a day | 6 months | ||
Onycomycosis : 200 mg twice daily for 7 days. Treatment with 2 one-week courses is recommended for fingernail infections and 3 one weeks courses for toenail infections. The one-week courses are always separated by a 3-week drug-free interval. Clinical response will become evident as the nail regrows, following discontinuation of the treatment.
Intraconazole Onychomycosis Dosing Schedule
| Pulse 1* | Pulse
2* |
Pulse 3* | |||||||
| Site of Onychomycosis | Week
1 |
Week
2 |
Week
3 |
Week
4 |
Week
5 |
Week
6 |
Week
7 |
Week
8 |
Week
9 |
| Toenails with/without fingernail involvement | 200 mg BID for 7 days | Itraconazole – free weeks | 200 mg BID for 7 days | Itraconazole – free weeks | 200 mg BID for 7 days | ||||
| Fingernails only | 200 mg BID for 7 days | Itraconazole – free weeks | 200 mg BID for 7 days | ||||||
* pulse = 1 week course of treatment
CONTRAINDICATIONS :
Itraconazole is contraindicated for :
- Patients who have shown hypersensitivity to Itraconazole or its excipients. Use with caution in prescribing to patients with hypersensitivity to other azoles.
- Treatment in pregnant women or in women contemplating pregnancy. If Itraconazole is given to women of childbearing potential, she must prevent pregnancy, effective contraception should be continued until one menstruation cycle following the end of treatment.
- Coadministration of Pimozide, Quinidine, Dofetilide, Cisapride, Mizolastine, Astemizole, Terfenadine, Triazolam or oral Midazolam.
- HMG-CoA reductase inhibitors metabolized by the CYP3A4 enzyme system (e.g., Lovastatin, Simvastatin) during Itraconazole therapy.
WARNINGS AND PRECAUTIONS :
- Itraconazole has been shown to have a negative inotropic effect and has been associated with reports of CHF (Congestive Heart Failure). Itraconazole should not be given to patients with evidence of ventricular dysfunction such as CHF or a history of CHF except its benefit is much greater than its risk and still concerning in disease, regimen dose, the risk factor of CHF. 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 CHF, should be freated 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, discontinue administration.
- Itraconazole is predominantly metabolized in the liver. The terminal half-life of Itraconazole in cirrhotic patients is somewhat prolonged. A decrease in the oral bioavailability of Itraconazole from Itraconazole capsules was observed in cirrhotic patient; this can also be expected with the oral solution. It is advisable to monitor Itraconazole plasma concentrations and to adapt the dose when necessary. In patients with raised liver enzymes or an active liver disease or who have experienced liver toxicity with other drugs, do not start treatment unless the expected benefit exceeds the risk of hepatic injury. In such cases, liver enzyme monitoring is necessary.
- It is advisable to monitor liver function in patients receiving continuous treatment of > 1 month and promptly in patients developing symptoms suggestive of hepatitis (e.g., anorexia, nausea, vomiting, fatigue, abdominal pain, dark urine).
- Discontinue if neuropathy occurs that may be attributable to Itraconazole capsules.
- Absorption of Itraconazole from the capsules is impaired when gastric acidity is decrease. In patients also receiving acid-neutralizing medicines (e.g., Aluminium hydroxide), these should be given at least 2 hours after the intake of Itraconazole capsules. In patients with achlorhydria, such as certain AIDS patients on acid secretion suppressors (e.g., H2 antagonists, Proton Pump Inhibitors), it is advisable to give Itraconazole capsules with a cola beverage.
- Itraconazole is excreted in breast milk; therefore it is not recommended to use this drug during lactation except its benefit exceed the risk or advise the patient to discontinue nursing while taking Itraconazole.
- Safety and efficacy in children have not been established. Therefore, not recommended to be given to children except its benefit is much greater than the risk.
- Renal insufficient : Bioavailability of Itraconazole is lower than normal patient. Monitoring of plasma concentration and dose adjustment may be needed.
- Use with caution for patients with hypersensitivity of azole.
DRUG INTERACTIONS :
- Concomitant use of Itraconazole and drugs metabolized by CYP3A4, may increase the plasma concentrations of these drugs. These elevated plasma concentrations may increase or prolong both therapeutic and adverse effects of these drugs. Whenever possible, plasma concentrations of these drugs should be monitored and dosage adjustments made after concomitant Itraconazole therapy is initiated.
- Inducers of CYP3A4 may decrease the plasma concentrations of Itraconazole. Itraconazole may not be effective in patients concomitantly taking Itraconazole and one of these drugs. Therefore, administration of these drugs with Itraconazole is not recommended.
- Other inhibitors of CYP3A4 may increase the plasma concentrations of Itraconazole. Patients who must take Itraconazole concomitantly with one of these drugs should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of Itraconazole.
Following is the list of drugs which influence or be influenced by Itraconazole :
| Decrease plasma concentration of Itraconazole : | ||
| Anticonvulsants | Carbamazepine,
Phenobarbital, Phenytoin |
Carbamazepine, Phenobarbital, Phenytoin are all inducers of CYP3A4.
Although interactions with Carbamazepine and Phenobarbital have not been studied, concomitant administration of Itraconazole and these drugs would be expected to result in decreased plasma concentrations of Itraconazole. |
| Antimycobacterials | Isoniazid, Rifabutin, Rifampin | Rifabutin is metabolized in part by CYP3A4 so can reduce plasma concentration of Itraconazole. This is similar as Isoniazid and Rifampin. |
| Gastric acid suppressors/neutralizers | Antacids, H2-reseptor antagonis, Proton pump Inhibitor | Absorption of Itraconazole is impaired when gastric acid production is decreased. Solving : Take Itraconazole with cola baverage during concomitant use with H2-reseptor antagonist. Antacids should be administered 1 hour before or 2 hours after take Itraconazole. |
| Non-nucleoside reverse transcriptase inhibitor | Nevirapine | Nevirapine is an inducer of CYP3A4. It induces the metabolism of Ketoconazole, significantly reducing the bioavailability of Ketoconazole. Because of the similarities between Ketoconazole and Itraconazole, concomitant administration of Itraconazole and Nevirapine is not recommended. |
| Increase plasma concentration of Itraconazole | ||
| Macroline antibiotics | Clarithromycin, Erithromycin | Erythromycin and Clarithromycin are known inhibitors of CYP3A4 and may increase plasma concentrations of Itraconazole. |
| Protease inhibitors | Indinavir, Ritonavir | |
| Drug plasma concentration increased by Itraconazole | ||
| Antiarrhythmics | Digoxin, Dofetilide, Quinidine, Disopyramide | Concomitant use with Itraconazole can increase plasma concentration of antiarrhytmics which could result in serious cardiovascular events. Therefore, concomitant use of this drug with Itraconazole is contraindicated. |
| Anticonvulsants | Carbamazepine | Concomitant use with Itraconazole can inhibit metabolism of Carbamazepine. |
| Antimycobacterials | Rifabutin | ltraconazole can inhibit metabolism of Rifabutin. |
| Antineoplastics | Busulfan, Docetaxel, Vinca alkaloids | Itraconazole can inhibit metabolism of Busulfan, Docetaxel, Vinca Alkaloid. |
| Antipsychotics | Pimozide | Concomitant use with Itraconazole can cause serious cardiovascular events. It is contraindicated to use this drug with Itraconazole concomitantly. |
| Benzodiazepines | Alprazolam, Diazepam, Midazolam, Triazolam | Itraconazole can increase plasma concentration of benzodiazepine so prolong its hypnotic and sedative effects. Concomitant use is contraindicated. |
| Calcium channel blockers | Dihydropyridine, Verapamil | Concomitant use with ltraconazole can cause oedema. Ca channel blocker has negative inotropic effect which may be additive to those of Itraconazole. |
| Gastrointestinal motility agents | Cisapride | Plasma concentration of Cisapride can be increased so can cause serious cardiovascular events. |
| HMG CoA-reductase inhibitor | Atorvastatin, Cerivastatin, Lovastatin, Simvastatin | Itraconazole inhibits metabolism of Atorvastatin, Cerivastatin, Lovastatin and Simvastatin. Concomitant use is contraindicated. |
| Immunosuppressants | Cyclosporine, Tacrolimus, Sirolimus | Concomitant use with Itraconazole can increase plasma concentration of immunosupresant such as Cyclosporine, Tacrolimus, Sirolimus. |
| Protease inhibitors | Indinavir, Ritonavir, Saquinavir | Itraconazole increases plasma concentration of protease inhibitor. |
| Other | Levacetylmethadol (Levomethadyl), ergot alkaloids, Halofantrine, Alfentanil, Buspirone, Methylprednisolone, Budesonide, Dexamethasone, Trimetrexate, Warfarin, Cilostazol, Eletriptan. | |
ADVERSE REACTIONS :
Dyspepsia; epigastric pain; upset stomach; vomiting; pyrosis; diarrhea; gastritis; flatulence/meteorism; constipation; decreased appetite; other gastric complaints; dizziness; faintness; somnolence; vertigo; pruritus; rash; fatigue; fever; edema; bronchitis/bronchospasm; coughing; dyspnea; rhinitis; sinusitis; increase in liver enzymes; abnormal liver function tests; jaundice; hepatitis; chirrosis; hepatocellular damage; chest pain; hypertension; hypokalemia; allergic reactions, including rash, pruritus, urticaria, angioedema and in rare instances, anaphylaxis, Steven-Johnson Syndrome, CHF, pulmonary edema, alopecia, hypertriglyceridemia, menstrual disorder, neutropenia and isolated cases of neuropathy.
PRESENTATION :
Itraconazole Capsule 100 mg Box, 3 strips @ 10 capsules Reg. No. GKL0402337001A1
STORAGE :
STORE BELOW 30ºC, PROTECT FROM LIGHT
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
