Isosorbidedinitraat CF may be available in the countries listed below.
Isosorbide Dinitrate is reported as an ingredient of Isosorbidedinitraat CF in the following countries:
International Drug Name Search
Fexofenadina Clorhidrato may be available in the countries listed below.
Fexofenadine hydrochloride (a derivative of Fexofenadine) is reported as an ingredient of Fexofenadina Clorhidrato in the following countries:
International Drug Name Search
Leuplin may be available in the countries listed below.
Leuprorelin acetate (a derivative of Leuprorelin) is reported as an ingredient of Leuplin in the following countries:
International Drug Name Search
Dermobarrina may be available in the countries listed below.
Benzalkonium chloride (a derivative of Benzalkonium) is reported as an ingredient of Dermobarrina in the following countries:
International Drug Name Search
Co-Salt may be available in the countries listed below.
Potassium Chloride is reported as an ingredient of Co-Salt in the following countries:
International Drug Name Search
Solmox may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Solmox in the following countries:
International Drug Name Search
Clusivol may be available in the countries listed below.
Ascorbic Acid is reported as an ingredient of Clusivol in the following countries:
International Drug Name Search
Calcium Folinate is reported as an ingredient of Leucovorin Calcium in the following countries:
Folinic Acid is reported as an ingredient of Leucovorin Calcium in the following countries:
International Drug Name Search
Lovacol may be available in the countries listed below.
Lovastatin is reported as an ingredient of Lovacol in the following countries:
International Drug Name Search
Badyket may be available in the countries listed below.
Bemiparin Sodium is reported as an ingredient of Badyket in the following countries:
International Drug Name Search
Real One may be available in the countries listed below.
Aripiprazole is reported as an ingredient of Real One in the following countries:
International Drug Name Search
Regrace may be available in the countries listed below.
Quinapril is reported as an ingredient of Regrace in the following countries:
International Drug Name Search
Do not administer Onmel for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. When itraconazole was administered intravenously to dogs and healthy human volunteers, negative inotropic effects were seen. If signs or symptoms of congestive heart failure occur during administration of Onmel, discontinue administration. [See Contraindications (4), Warnings and Precautions (5), Drug Interactions (7), and Clinical Pharmacomogy (12)]
Drug Interactions: Co-administration of cisapride, pimozide, quinidine, dofetilide, levacetylmethadol (levomethadyl), felodipine, oral midazolam, nisoldipine, triazolam, lovastatin, simvastatin, ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine) or methadone with Onmel is contraindicated. Onmel, a potent cytochrome P450 3A4 isoenzyme system (CYP3A4) inhibitor, may increase plasma concentrations of drugs metabolized by this pathway. Serious cardiovascular events, including QT prolongation, torsades de pointes, ventricular tachycardia, cardiac arrest, and/or sudden death have occurred in patients using cisapride, pimozide, levacetylmethadol (levomethadyl), methadone or quinidine concomitantly with itraconazole and/or other CYP3A4 inhibitors. [See Contraindications (4), Warnings and Precautions (5), and Drug Interactions (7)]
Onmel is indicated for the treatment of onychomycosis of the toenail due to Trichophyton rubrum or T. mentagrophytes in non-immunocompromised patients. Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis. [See Contraindications (4), Warnings and Precautions (5), Drug Interactions (7), and Clinical Pharmacology (12).]
Onmel should be taken with a full meal at the same time each day. The recommended dose is 200 mg (one tablet) once daily for 12 consecutive weeks.
Use in Patients with Renal Impairment:
Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when Onmel is administered to patients with renal impairment. [See Clinical Pharmacology (12) and Warnings and Precautions (5).]
Use in Patients with Hepatic Impairment:
Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when Onmel is administered to patients with hepatic impairment. [See Clinical Pharmacology (12) and Warnings and Precautions (5).]
Onmel contain 200 mg of itraconazole, as a white to slightly grey, oblong, biconvex tablet engraved with “BARRIER” on one side and “It 200” on the other side.
Congestive Heart Failure: Do not administer Onmel for the treatment of onychomycosis in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF. [See Warnings and Precautions (5), Drug Interactions (7), and Clinical Pharmacology (12).]
Drug Interactions: Concomitant administration of Onmel and certain drugs that are metabolized by the cytochrome P450 3A4 isoenzyme system (CYP3A4) or where gastrointestinal absorption is regulated by P-gp may result in increased plasma concentrations of those drugs, leading to potentially serious and/or life-threatening adverse events.
Co-administration of cisapride, dofetilide, ergot alkaloids such as dihydroergotamine, ergotamine, ergometrine (ergonovine), and methylergometrine (methylergonovine), felodipine, levacetylmethadol (levomethadyl), lovastatin, methadone, oral midazolam, nisoldipine, pimozide, quinidine, simvastatin, and triazolam with Onmel is contraindicated.
Do not administer Onmel for the treatment of onychomycosis to pregnant patients or to women contemplating pregnancy.
Anaphylaxis and hypersensitivity have been reported with use of itraconazole. Onmel is contraindicated for patients who have shown hypersensitivity to itraconazole products.
Cases of CHF, peripheral edema, and pulmonary edema have been reported with itraconazole administration among patients being treated for onychomycosis and/or systemic fungal infections. [See Contraindications (4), Warnings and Precautions (5), and Clinical Pharmacology (12).]
Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using cisapride, pimozide, levacetylmethadol (levomethadyl), methadone, or quinidine concomitantly with itraconazole and/or other CYP3A4 inhibitors. Concomitant administration of these drugs with Onmel is contraindicated. [See Boxed Warning, Contraindications (4), Warnings and Precautions (5), and Drug Interactions (7).]
Onmel should not be administered in patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF.
Itraconazole has been shown to have a negative inotropic effect. When itraconazole was administered intravenously to anesthetized dogs, a dose-related negative inotropic effect was documented. In a healthy volunteer study of itraconazole injection, transient, asymptomatic decreases in left ventricular ejection fraction were observed using gated SPECT imaging; these resolved before the next infusion, 12 hours later.
For patients with risk factors for congestive heart failure, physicians should carefully review the risks and benefits of Onmel therapy. 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 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 Onmel, discontinue administration.
Itraconazole has been associated with rare cases of serious hepatotoxicity, including liver failure and death. Some of these cases had neither pre-existing liver disease nor a 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 hepatotoxicity, treatment should be discontinued immediately and liver function testing performed.
In patients with elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment with itraconazole is not recommended. Liver function monitoring should be done in patients with pre-existing hepatic function abnormalities or those who have experienced liver toxicity with other medications and should be considered in all patients receiving Onmel.
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 Onmel and nisoldipine is contraindicated.
If neuropathy occurs that may be attributable to Onmel, the treatment should be discontinued.
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. [See Boxed Warning, Warnings and Precautions (5), and Drug Interactions (7).] The hearing loss usually resolves when treatment is stopped, but can persist in some patients.
Because clinical trials are conducted under widely varying conditions, the adverse reaction rate observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Patients in the trial for toenail onychomycosis were treated with a dosing regimen of 200 mg once daily for 12 consecutive weeks.
The most commonly reported adverse reaction leading to discontinuation of Onmel was increased hepatic enzyme (6 subjects, 1.0%), followed by dizziness (3 subjects, 0.5%). No other adverse reaction leading to discontinuation occurred in more than one subject.
The table below lists all adverse reactions reported by at least 1% of patients who received Onmel during 12 weeks of treatment:
BODY SYSTEM/ADVERSE REACTION | Incidence (%) Onmel (N = 582) | Incidence (%) Placebo tablet (N = 191) |
INFECTIONS AND INFESTATIONS Upper respiratory tract infections Bacteriuria Urinary tract infection | 6.0% 1.4% 1.0% | 7.3% 1.6% 0.5% |
INVESTIGATIONS Hepatic enzymes increased Electrocardiogram abnormal | 2.9% 1.4% | 0.0% 1.6% |
EAR AND LABYRINTH DISORDERS Hypoacusis | 3.3% | 3.1% |
NERVOUS SYSTEM DISORDERS Headache Dizziness | 2.2% 1.2% | 1.6% 0.0% |
GASTROINTESTINAL DISORDERS Abdominal pain or discomfort Diarrhea Nausea | 1.7% 1.7% 1.7% | 2.6% 3.1% 1.6% |
GENERAL DISORDERS OF ADMINISTRATION SITE CONDITIONS Fatigue | 1.5% | 2.6% |
CARDIAC DISORDERS Sinus Bradycardia | 1.0% | 0.0% |
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS Cough Pharyngolaryngeal pain | 1.2% 1.0% | 0.0% 0.5% |
MUSCULOSCELETAL AND CONNECTIVE TISSUE DISORDERS Back pain | 1.2% | 2.1% |
The following adverse reactions have been identified during post-approval use of itraconazole (all formulations) and are listed in Table 2 below. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establishing a causal relationship to drug exposure.
| Blood and lymphatic system disorders: | Leaukopenia, neutropenia, thrombocytopenia |
| Immune system disorders: | Anaphylaxis; anaphylactic, anaphylactoid and allergic reactions; serum sickness; angioneurotic edema |
| Metabolism and nutritional disorders: | Hypertriglyceridemia, hypokalemia |
| Nervous system disorders: | Peripheral neuropathy, paresthesia, hypoesthesia, headache, dizziness |
| Eye disorders: | Visual disturbances, including vision blurred and diplopia |
| Ear and labyrinth disorders: | Transient or permanent hearing loss, tinnitus |
| Cardiac disorders: | Congestive heart failure |
| Respiratory, thoracic and mediastinal disorders: | Pulmonary edema |
| Gastrointestinal disorders: | Abdominal pain, vomiting, dyspepsia, nausea, diarrhea, constipation, dysgeusia |
| Hepato-biliary disorders: | Serious hepatotoxicity (including some cases of fatal acute liver failure), hepatitis, reversible increases in hepatic enzymes |
| Skin and subcutaneous tissue disorders: | Toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, leukocytoclastic vasculitis, erythema multiforme, alopecia, photosensitivity, rash, urticaria, pruritus |
| Musculoskeletal and connective tissue disorders: | Myalgia, arthralgia |
| Renal and urinary disorders: | Urinary incontinence, pollakiuria |
| Reproductive system and breast disorders: | Menstrual disorders, erectile dysfunction |
General disorders and administration site conditions: | Peripheral edema |
Itraconazole and its major metabolite, hydroxy-itraconazole, are strong inhibitors of the cytochrome P450 3A4 isoenzyme system (CYP3A4). Therefore, concomitant administration of Onmel and certain drugs metabolized by the cytochrome CYP3A4 may result in increased plasma concentrations of those drugs due to decreased elimination, leading to potentially serious and/or life-threatening adverse events. Itraconazole is also an inhibitor of P-glycoprotein (P-gp) transporter and may result in increased plasma concentrations of drugs whose gastrointestinal absorption is regulated by P-gp. Whenever possible, plasma concentrations of these drugs should be monitored, and dosage adjustments made after concomitant Onmel therapy is initiated. When appropriate, clinical monitoring for signs or symptoms of increased or prolonged pharmacologic effects is advised. Upon discontinuation, itraconazole plasma concentrations decline gradually (especially in patients with hepatic cirrhosis or in those receiving CYP3A4 inhibitors). This is particularly important when initiating therapy with drugs whose metabolism is affected by itraconazole.
Inducers of CYP3A4 may decrease the plasma concentrations of itraconazole. Onmel may not be effective in patients concomitantly taking Onmel and one of these drugs. Therefore, administration of these drugs with Onmel is not recommended.
Inhibitors of CYP3A4 may increase the plasma concentrations of itraconazole. Patients who must take Onmel concomitantly with one of these drugs should be monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of Onmel.
| |
| Drug plasma concentration increased by itraconazole | |
| Antiarrhythmics | digoxin, dofetilide, quinidine, disopyramide |
| Anticonvulsants | carbamazepine |
| Anti-HIV Agents | indinavir, ritonavir, saquinavir, maraviroc |
| Antineoplastics | busulfan, docetaxel, vinca alkaloids |
| Antipsychotics | pimozide |
| Benzodiazepines | alprazolam, diazepam, midazolam†, triazolam |
| Calcium Channel Blockers | dihydropyridines (including nisoldipine and felodipine), verapamil |
| Gastrointestinal Motility Agents | cisapride |
| HMG CoA-Reductase Inhibitors | atorvastatin, cerivastatin, lovastatin, simvastatin |
| Immunosuppressants | Cyclosporine, tacrolimus, sirolimus |
| Oral Hypoglycemics | oral hypoglycemics (repaglinide) |
| Opiate Analgesics | fentanyl, levacetylmethadol (levomethadyl), methadone |
| Polyene Antifungals | amphotericin B |
| Other | ergot alkaloids, halofantrine, alfentanil, buspirone, methylprednisolone, budesonide, dexamethasone, fluticasone, warfarin, cilostazol, eletriptan, fexofenadine, loperamide |
| Decrease plasma concentration of itraconazole | |
| Anticonvulsants | carbamazepine, phenobarbital, phenytoin |
| Anti-HIV Agents | nevirapine, efavirenz |
| Antimycobacterials | isoniazid, rifabutin, rifampin |
| Gastric Acid Suppressors/Neutralizers | antacids, H2-receptor antagonists, proton pump inhibitors |
| Increase plasma concentration of itraconazole | |
| Macrolide Antibiotics | clarithromycin, erythromycin |
| Anti-HIV Agents | indinavir, ritonavir |
| |
| Antipsychotics | pimozide |
| Antiarrhythmics | dofetilide, quinidine |
| Benzodiazepines | oral midazolam†, triazolam |
| Calcium Channel Blockers | Nisoldipine, felodipine |
| Ergot Alkaloids | dihydroergotamine, ergotamine, ergometrine (ergonovine), methylergometrine (methylergonovine) |
| Gastrointestinal Motility Agents | cisapride |
| HMG CoA-Reductase Inhibitors | lovastatin, simvastatin |
| Opiate Analgesics | levacetylmethadol (levomethadyl), methadone |
Antiarrhythmics
The Class IA antiarrhythmic, quinidine and class III antiarrhythmic, dofetilide are known to prolong the QT interval. Co-administration of quinidine or dofetilide with itraconazole may increase plasma concentrations of quinidine or dofetilide, which could result in serious cardiovascular events. Therefore, concomitant administration of Onmel and quinidine or dofetilide is contraindicated. [See Boxed Warning, Contraindications (4), and Warnings and Precautions (5).]
The Class IA antiarrhythmic, disopyramide has the potential to increase the QT interval at high plasma concentrations. Caution is advised when Onmel and disopyramide are administered concomitantly.
Concomitant administration of digoxin and itraconazole has led to increased plasma concentrations of digoxin via inhibition of P-glycoprotein.
Anticonvulsants
Carbamazepine, phenobarbital, and phenytoin are all inducers of CYP3A4. Reduced plasma concentrations of itraconazole were reported when itraconazole was administered concomitantly with phenytoin. Although interactions with carbamazepine and phenobarbital have not been studied, concomitant administration of Onmel and these drugs would be expected to result in decreased plasma concentrations of itraconazole. In addition, in vivo studies have demonstrated an increase in plasma carbamazepine concentrations in subjects concomitantly receiving ketoconazole. Although there are no data regarding the effect of itraconazole on carbamazepine metabolism, because of the similarities between ketoconazole and itraconazole, concomitant administration of Onmel and carbamazepine may inhibit the metabolism of carbamazepine.
Anti-HIV Agents
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI) such as nevirapine and efavirenz are inducers of CYP3A4. Human pharmacokinetic studies have shown that efavirenz, when concomitantly administered with itraconazole, greatly decreased serum concentrations of itraconazole and hydroxyl-itraconazole. Concomitant use of Onmel and efavirenz is not recommended.
In vivo studies have shown that nevirapine induces the metabolism of ketoconazole, significantly reducing the bioavailability of ketoconazole. Studies involving nevirapine and itraconazole have not been conducted. However, because of the similarities between ketoconazole and itraconazole, concomitant administration of Onmel and nevirapine is not recommended.
Concomitant administration of Onmel and protease inhibitors metabolized by CYP3A4, such as indinavir, ritonavir, and saquinavir, may increase plasma concentrations of these protease inhibitors. In addition, concomitant administration of Onmel and indinavir and ritonavir (but not saquinavir) may increase plasma concentrations of itraconazole. Caution is advised when Onmel and protease inhibitors must be given concomitantly.
Concomitant administration of Onmel and maraviroc has been reported to increase plasma concentration of maraviroc. The dose of maraviroc should be decreased to 150 mg twice daily when given in combination with itraconazole.
Antimycobacterials
Drug interaction studies have demonstrated that plasma concentrations of azole antifungal agents and their metabolites, including itraconazole and hydroxyitraconazole, were significantly decreased when these agents were given concomitantly with rifabutin or rifampin. In vivo data suggest that rifabutin is metabolized in part by CYP3A4. Onmel may inhibit the metabolism of rifabutin. Although no formal study data are available for isoniazid, similar effects should be anticipated. Therefore, the efficacy of Onmel could be substantially reduced if given concomitantly with one of these agents and co-administration is not recommended.
Antineoplastics
Onmel may inhibit the metabolism of busulfan, docetaxel, and vinca alkaloids.
Antipsychotics
Pimozide is known to prolong the QT interval and is partially metabolized by CYP3A4. Co-administration of pimozide with itraconazole could result in serious cardiovascular events. Therefore, concomitant administration of Onmel and pimozide is contraindicated. [See Boxed Warning, Contraindications (4), and Warnings and Precautions (5).]
Increases in plasma aripiprazole concentrations have been demonstrated in subjects concomitantly receiving ketoconazole, requiring a reduction of the aripiprazole dose. Because of the similarities between ketoconazole and itraconazole, a similar dose reduction for aripiprazole is recommended when patients concomitantly receive itraconazole and aripiprazole.
Benzodiazepines
Concomitant administration of itraconazole and alprazolam, diazepam, oral midazolam, or triazolam could lead to increased plasma concentrations of these benzodiazepines. Increased plasma concentrations could potentiate and prolong hypnotic and sedative effects. Concomitant administration of Onmel and oral midazolam or triazolam is contraindicated. [See Contraindications (4), and Warnings and Precautions (5).] If midazolam is administered parenterally, special precaution and patient monitoring is required since the sedative effect may be prolonged.
Calcium Channel Blockers
Calcium channel blockers can have a negative inotropic effect which may be additive to those of itraconazole; itraconazole can inhibit the metabolism of calcium channel blockers such as dihydropyridines (e.g., nifedipine, nisoldipine, and felodipine) and verapamil. Therefore, caution should be used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHF.
Concomitant administration of Onmel and nisoldipine results in clinically significant increases in nisoldipine plasma concentrations, which cannot be managed by dosage reduction, therefore the concomitant administration of Onmel and nisoldipine is contraindicated. A clinical study showed that felodipine exposure was increased by co-administration of itraconazole, resulting in approximately 6-fold increase in the AUC and 8-fold increase in the Cmax. The concomitant use of Onmel and felodipine is contraindicated. [See Contraindications (4), Warnings and Precautions (5), Drug Interactions (7), and Clinical Pharmacology (12).]
Edema has been reported in patients concomitantly receiving itraconazole and dihydropyridine calcium channel blockers. Appropriate dosage adjustment may be necessary.
Gastric Acid Suppressors/Neutralizers
Reduced plasma concentrations of itraconazole were reported when administered concomitantly with H2-receptor antagonists. Studies have shown that absorption of itraconazole is impaired when gastric acid production is decreased. Onmel should be administered with a cola beverage if the patient has achlorhydria or is taking H2-receptor antagonists or other gastric acid suppressors. It is advised that antacids be administered at least 1 hour before or 2 hours after administration of Onmel. In a clinical study, when itraconazole capsules were administered with omeprazole (a proton pump inhibitor), the bioavailability of itraconazole was significantly reduced.
Gastrointestinal Motility Agents
Coadministration of itraconazole with cisapride can elevate plasma cisapride concentrations, which could result in serious cardiovascular events. Therefore, concomitant administration of Onmel with cisapride is contraindicated. [See Boxed Warning, Contraindications (4), and Warnings and Precautions (5).]
3-Hydroxy-3-Methyl-Glutaryl CoA-Reductase Inhibitors
Human pharmacokinetic data suggest that itraconazole inhibits the metabolism of atorvastatin, cerivastatin, lovastatin, and simvastatin, which may increase the risk of skeletal muscle toxicity, including rhabdomyolysis. Concomitant administration of Onmel with 3-Hydroxy-3-Methyl-Glutaryl (HMG) CoA-Reductase inhibitors, such as lovastatin and simvastatin, is contraindicated. [See Contraindications (4), and Warnings and Precautions (5).]
Immunosuppressants
Concomitant administration of Onmel and cyclosporine or tacrolimus has led to increased plasma concentrations of these immunosuppressants. Similarly, concomitant administration of Onmel and sirolimus could increase plasma concentrations of sirolimus.
Monitoring of blood concentrations of cyclosporine, tacrolimus, or sirolimus are recommended when Onmel are coadministered with these immunosuppressants and appropriate dosage adjustments should be made.
Macrolide Antibiotics
Erythromycin and clarithromycin are known inhibitors of CYP3A4 (See Table 3) and may increase plasma concentrations of itraconazole.
Oral Hypoglycemic Agents
Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. A human pharmacokinetic study showed that co-administration with itraconazole and a single dose of repaglinide (on the third day of a regimen of 200 mg initial dose, twice-daily 100 mg itraconazole) resulted in a 1.4-fold higher repaglinide AUC. Blood glucose concentrations should be carefully monitored when Onmel and oral hypoglycemic agents are co-administered.
Polyenes Antifungal Agents
Prior treatment with itraconazole, like other azoles, may reduce or inhibit the activity of polyenes such as amphotericin B. However, the clinical significance of this drug effect has not been clearly defined.
Opiate Analgesics
Levacetylmethadol (levomethadyl) and methadone are known to prolong the QT interval and are metabolized by CYP3A4. Co-administration of methadone or levacetylmethadol with itraconazole could result in serious cardiovascular events. Therefore, concomitant administration of Onmel and methadone or levacetylmethadol are contraindicated. Fentanyl plasma concentrations could be increased or prolonged by concomitant use of itraconazole and may cause potentially fatal respiratory depression.
In vitro data suggest that alfentanil is metabolized by CYP3A4. Administration with itraconazole may increase plasma concentrations of alfentanil.
Other
Teratogenic effects. Pregnancy Category C
There are no adequate and well-controlled clinical trials in the pregnant women with itraconazole. However, cases of congenital abnormalities have been reported with itraconazole drug products in post-marketing reports. Therefore, Onmel should not be administered to pregnant women, women planning pregnancy, or women of child bearing potential unless these onychomycosis patients are using effective contraception measures to prevent pregnancy. Effective contraceptive measures should continue throughout the treatment period and for two months thereafter. Onmel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Itraconazole produced a significant dose-related increase in maternal toxicity, embryotoxicity, and teratogenicity in rats at dose levels of 40-160 mg/kg/day (2-10 times the maximum recommended human dose [MRHD], based on mg/m2/day comparisons), and in mice at 80 mg/kg/day (2 times MRHD, based on mg/m2/day comparisons). Teratogenic changes in rats included major skeletal defects; encephalocele and/or macroglossia developed in mice.
Itraconazole is excreted in human milk; therefore, the expected benefits of Onmel therapy for the mother should be weighed against the potential risk from exposure of itraconazole to the infant.
The safety and effectiveness of Onmel in pediatric patients have not been established. No pharmacokinetic data on Onmel are available in children.
Onmel was evaluated in 42 of 593 subjects (7.1%) greater than 65 years of age.
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. [See Boxed Warning, Contraindications (4), Drug Interactions (7), and Warnings and Precautions (5).] Itraconazole should be used with care in elderly patients. [See Warnings and Precautions (5).]
Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when Onmel is administered to patients with renal impairment. [See Clinical Pharmacology (12) and Dosage and Administration (2).]
Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when Onmel is administered to patients with hepatic impairment. [See Clinical Pharmacology (12) and Dosage and Administration (2).]
Itraconazole is not removed by dialysis. In the event of accidental overdosage, supportive measures, including gastric lavage with sodium bicarbonate, should be employed.
Onmel (itraconazole) is a synthetic triazole antifungal agent for oral use. Itraconazole is a 1:1:1:1 racemic mixture of four diastereomers (two enantiomeric pairs), each possessing three chiral centers. It may be represented by the following structural formula and nomenclature:
(±) - cis - 4 - [4 - [4 - [4[[2 - (2,4 - dichlorophenyl) - 2 - (1H - 1,2,4 - triazol - 1 - ylmethyl) - 1,3 - dioxolane - 4 - yl]methoxy]phenyl] - 1 - piperazinyl]phenyl] - 2,4 - dihydro - 2 - (1 - methylpropyl) - 3H - 1,2,4 - triazol - 3 - one
Itraconazole has a molecular formula of C35H38Cl2N8O4 and a molecular weight of 705.64. It is a white to slightly yellowish powder. It is insoluble in water, very slightly soluble in alcohols, and freely soluble in dichloromethane. It has a pKa of 3.70 (based on extrapolation of values obtained from methanolic solutions) and a log (n-octanol/water) partition coefficient of 5.66 at pH 8.1.
Each Onmel is formulated for melt extrusion technology and contains 200 mg of itraconazole and the following inactive ingredients: colloidal silicon dioxide, crospovidone, hydrogenated vegetable oil, hypromellose, lactose, microcrystalline cellulose, magnesium stearate, propylene glycol, talc, and titanium dioxide.
Itraconazole, an azole, is an antifungal agent [See Clinical Pharmacology (12) and Microbiology(12.4)].
The oral bioavailability of itraconazole is increased when Onmel is taken with a FDA standard high-fat meal. The pharmacokinetic parameters of itraconazole and hydroxy-itraconazole after administration of one Onmel to 9 male and 9 female healthy subjects in fasting and in fed conditions are presented in the table below:
| ||||
| Itraconazole | Hydroxy-itraconazole | |||
| Fed | Fasted | Fed | Fasted | |
| Cmax (ng/mL) | 213 ± 117† | 162 ± 107 | 332 ± 118 | 264 ± 109 |
| Tmax (hours) | 4.6 ± 2.2 | 2.9 ± 0.8 | 5.7 ± 2.6 | 3.4 ± 0.8 |
| AUC0-∞ (μg.h/mL) | 3.34 ± 1.98 | 2.27 ± 1.44 | 7.05 ± 3.94 | 4.58 ± 2.80 |
The steady-state pharmacokinetics of itraconazole and hydroxy-itraconazole were analyzed after oral dosing of 16 healthy volunteers with one Onmel following a moderate-fat breakfast once daily for 14 days in an open-label study. Mean maximum plasma levels of itraconazole and hydroxy-itraconazole increased from Day 1 to Day 14 by approximately 6- and 4-fold, respectively. The respective pharmacokinetic parameters from this study are reflected in the table below:
Allergan may be available in the countries listed below.
Diphenhydramine hydrochloride (a derivative of Diphenhydramine) is reported as an ingredient of Allergan in the following countries:
International Drug Name Search
Fenolid may be available in the countries listed below.
Fenofibrate is reported as an ingredient of Fenolid in the following countries:
International Drug Name Search
Monopront may be available in the countries listed below.
Isosorbide Mononitrate is reported as an ingredient of Monopront in the following countries:
International Drug Name Search
Malidens may be available in the countries listed below.
Paracetamol is reported as an ingredient of Malidens in the following countries:
International Drug Name Search
Famotidine Healthypharm may be available in the countries listed below.
Cimetidine is reported as an ingredient of Famotidine Healthypharm in the following countries:
International Drug Name Search
Loxot may be available in the countries listed below.
Loxoprofen sodium salt (a derivative of Loxoprofen) is reported as an ingredient of Loxot in the following countries:
International Drug Name Search
Acido chenodessicolico may be available in the countries listed below.
Acido chenodessicolico (DCIT) is known as Chenodeoxycholic Acid in the US.
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
Alka-Prim may be available in the countries listed below.
Acetylsalicylic Acid is reported as an ingredient of Alka-Prim in the following countries:
International Drug Name Search
Munobal may be available in the countries listed below.
Felodipine is reported as an ingredient of Munobal in the following countries:
International Drug Name Search
Chlorhydrate de cyclopentolate may be available in the countries listed below.
Cyclopentolate hydrochloride (a derivative of Cyclopentolate) is reported as an ingredient of Chlorhydrate de cyclopentolate in the following countries:
International Drug Name Search
Fosfocrisolo may be available in the countries listed below.
Sodium Aurotiosulfate is reported as an ingredient of Fosfocrisolo in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
Benzylpenicillin potassium (a derivative of Benzylpenicillin) is reported as an ingredient of Penaqua in the following countries:
International Drug Name Search
Cotrim K-ratiopharm may be available in the countries listed below.
Sulfamethoxazole is reported as an ingredient of Cotrim K-ratiopharm in the following countries:
Trimethoprim is reported as an ingredient of Cotrim K-ratiopharm in the following countries:
International Drug Name Search
Trileptal is a brand name of oxcarbazepine, approved by the FDA in the following formulation(s):
A generic version of Trileptal has been approved by the FDA. However, this does not mean that the product will necessarily be commercially available - possibly because of drug patents and/or drug exclusivity. The following products are equivalent to Trileptal and have been approved by the FDA:
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Trileptal. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
Patents are granted by the U.S. Patent and Trademark Office at any time during a drug's development and may include a wide range of claims.
Respichlor may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Chlortetracycline hydrochloride (a derivative of Chlortetracycline) is reported as an ingredient of Respichlor in the following countries:
International Drug Name Search
Sunpraz may be available in the countries listed below.
Pantoprazole sodium (a derivative of Pantoprazole) is reported as an ingredient of Sunpraz in the following countries:
International Drug Name Search
Furosemid AbZ may be available in the countries listed below.
Furosemide is reported as an ingredient of Furosemid AbZ in the following countries:
International Drug Name Search
See also: Generic Verelan PM
Verelan is a brand name of verapamil, approved by the FDA in the following formulation(s):
Yes. The following products are equivalent to Verelan:
Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Verelan. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.
See also: About generic drugs.
There are no current U.S. patents associated with Verelan.
Carbamid Widmer may be available in the countries listed below.
Urea is reported as an ingredient of Carbamid Widmer in the following countries:
International Drug Name Search
In the US, Feostat (ferrous fumarate systemic) is a member of the drug class iron products and is used to treat Anemia Associated with Chronic Renal Failure, Iron Deficiency Anemia, Vitamin/Mineral Supplementation and Deficiency and Vitamin/Mineral Supplementation during Pregnancy/Lactation.
US matches:
Ferrous Fumarate is reported as an ingredient of Feostat in the following countries:
International Drug Name Search
Zocin may be available in the countries listed below.
Azithromycin is reported as an ingredient of Zocin in the following countries:
International Drug Name Search
Nifedipin Pliva may be available in the countries listed below.
Nifedipine is reported as an ingredient of Nifedipin Pliva in the following countries:
International Drug Name Search
Morphine Oral Solution may be available in the countries listed below.
Morphine sulphate pentahydrate (a derivative of Morphine) is reported as an ingredient of Morphine Oral Solution in the following countries:
International Drug Name Search
Apo-Lithium Carbonate may be available in the countries listed below.
Lithium carbonate (a derivative of Lithium) is reported as an ingredient of Apo-Lithium Carbonate in the following countries:
International Drug Name Search
In some countries, this medicine may only be approved for veterinary use.
Triflupromazine hydrochloride (a derivative of Triflupromazine) is reported as an ingredient of Vetame in the following countries:
International Drug Name Search
In the US, Commit (nicotine systemic) is a member of the drug class smoking cessation agents and is used to treat Smoking Cessation.
US matches:
Nicotine resinate (a derivative of Nicotine) is reported as an ingredient of Commit in the following countries:
International Drug Name Search
Generic Name: barium sulfate (Oral route, Rectal route)
BAR-ee-um SUL-fate
In the U.S.
In Canada
Available Dosage Forms:
Therapeutic Class: Diagnostic Agent, Radiological Contrast Media
Barium sulfate is a radiopaque agent. Radiopaque agents are used to help diagnose certain medical problems. Since radiopaque agents are opaque to (block) x-rays, the areas of the body in which they are localized will appear white on the x-ray film. This creates the needed distinction, or contrast, between one organ and other tissues. The contrast will help the doctor see any special conditions that may exist in that organ or part of the body.
Barium sulfate is taken by mouth or given rectally by enema. If taken by mouth, it makes the esophagus, the stomach, and/or the small intestine opaque to the x-rays so that they can be "photographed". If it is given by enema, the colon and/or the small intestine can be seen and photographed by x-rays.
The dose of barium sulfate will be different for different patients and depends on the type of test. The strength of the suspension and tablet is determined by how much barium they contain. Different tests will require a different strength and amount of suspension (some may require the tablet form), depending on the age of the patient, the contrast needed, and the x-ray equipment used.
Barium sulfate is to be used only by or under the direct supervision of a doctor.
In deciding to use a diagnostic test, any risks of the test must be weighed against the good it will do. This is a decision you and your doctor will make. Also, other things may affect test results. For this test, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Although there is no specific information comparing use of barium sulfate in children with use in other age groups, this agent is not expected to cause different side effects or problems in children than it does in adults.
This contrast agent has been used in older people and has not been shown to cause different side effects or problems in them than it does in younger adults.
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.
The presence of other medical problems may affect the use of this diagnostic test. Make sure you tell your doctor if you have any other medical problems, especially:
This section provides information on the proper use of a number of products that contain barium sulfate. It may not be specific to Readi-Cat. Please read with care.
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
Make sure to drink plenty of liquids after the test. Otherwise, barium sulfate may cause severe constipation.
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
See also: Readi-Cat side effects (in more detail)
The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.
The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.
Cefpodoxime Ratiopharm may be available in the countries listed below.
Cefpodoxime proxetil (a derivative of Cefpodoxime) is reported as an ingredient of Cefpodoxime Ratiopharm in the following countries:
International Drug Name Search
Fluconazol AL may be available in the countries listed below.
Fluconazole is reported as an ingredient of Fluconazol AL in the following countries:
International Drug Name Search
Magne may be available in the countries listed below.
Magnesium Citrate is reported as an ingredient of Magne in the following countries:
Magnesium Lactate is reported as an ingredient of Magne in the following countries:
Pyridoxine hydrochloride (a derivative of Pyridoxine) is reported as an ingredient of Magne in the following countries:
International Drug Name Search
Disprin may be available in the countries listed below.
Acetylsalicylic Acid is reported as an ingredient of Disprin in the following countries:
International Drug Name Search
Calcium Sandoz Junior may be available in the countries listed below.
Calcium Carbonate is reported as an ingredient of Calcium Sandoz Junior in the following countries:
International Drug Name Search
