Drug Interaction:
Azole anti-fungals include-
Fluconazole, Itraconazole, Ketoconazole, Miconazole, Econazole, Terconazole
Interacting drugs- summary
Intraconazole +
Astemazole / Terfenadine
Increased terfenadine plasma levels,resulting in life threatening
cardiac dysrhythmias and death. Co-admin with astemazole
have same effect. Avoid concurrent use
Calcium blockers
edema has occured with cocomittant use of itraconazole and
amlodipine, nifedipine
Cyclosporine + HMG CoA reductase inhibitors
Rhabdomyolysis has been noticed in patients receiving
HMG- CoA reductase inhibitors alone or concomittantly.
Reduce cyclosporine levels when using itraconazole
Digoxin
Increased digoxin level occur. Monitor digoxin levels initially and
frequently thereafter
Triazolam or Midozalam
coadmin has resulted in elevated plasma levles of midazolam
or triazolam. These agents should not be used concurrently
Quinidine
tinnitus and decreased hearing has occured
Sulfonylureas
hypoglycaemia may occur. Monitor blood glucose
Tacrolimus
coadmin has led to increased tracrolimus plasma concentrations
Warfarin
anticoagulant of warfarin may be enhanced.Monitor prothrombin time
Cisapride
Concurrent administration of ketoconazole with cisapride resulted in
markedly elevated cisapride concentration, prolonged QT intervals,
Therefore concomittant use is contraindicated
+ Itraconazole
H2 antagonists
reduced plasma itraconazole levels occur
Phenytoin + Itraconazole or Itraconazole + Phenytoin
reduced plasma itraconazole levels occur. Also phenytoin metabolism
may be altered
Rifampin
reduced plasma itraconazole levels occur
Indication:
Fungal infections
Azole anti-fungals include-
Fluconazole, Itraconazole, Ketoconazole, Miconazole, Econazole, Terconazole
Approved by FDA on Sept 11,1992
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Itraconazole Antifungal July 1993
Adverse Reaction:
GI-Nausea, vomiting, elevated liver enzymes, GI disorders, diarrhea, abdominal pain, anorexia Body as whole- edema,fatigue, fever, malaise, myalgia.
Cardiovascular- hypertension, orthostatic hypotension, vasculitis.
Dermatologic- rasg, pruritus
CNS- headache, dizziness/Verigo, libido decreased, somnolence
Miscellaneous- hepatic functionabnormal, hypokalemia, albuminuria, impotence
Frequently reported adverse events- allergic reactions, rash, pruritus, urticaria, angioedema, and in rare cases
Stevens-Johnson syndrome
Contra-Indications:
Coadmin of terfenadine, astemazole, cisapride, triazolam, or oral midazolam. Hypersen to the drug. Do not administer for treatment of onchomycosis to pregnant women or to women comtemplating pregnancy.
Special precautions:
Monitor hepatic enzme tests in patients with pre-existing hepatic disorders. Decreased gastric acidity.
Monitoring- monitor hepatic values in patients with pre-existing hepatic function abnormalites. Momitor hepatic enzyme test values periodically in all patients receiving continuous treatment for > 1 month or at any time patient develops signs or symptoms suggestive of liver dysfunction.
Decreased gastric acidity- under fasted conditions itraconazole absorption was decreased in presence of decreased gastric acidity. The absorption of itraconazole may be decreased with the concomittant administration of antacids or gastric secretion suppressors.
Warnings
Cultures- obtain specimen for fungal cultures and other relevent laboratory studies (wet mount, histopathology, serolgy) prior to therapy to isolate and identify causative organisms. Therapy may be instituted before the results of culture and other laboratory studies are known, However, once these results become available, adjust anti-infective therapy accordingly.
Hepatitis- if signs and symptoms consistent with liver disease that may be attributable to intraconazole discontinue the drug.
HIV- infected patients- because hypochlorhydria has occured in HIV-infected individuals, the absorption of itraconazole in these pastients may be decreased.
Pregnancy- use in pregnancy for systemic fungal infections only if the benefit outweighs the potential risks.
Lactation- itraconazole is excreted in breast milk, therefore do not administer to a nursing woman.
Children- safety and efficacy have not been established
Dosages/ Overdosage Etc:
Approved by FDA on Sept 11,1992
Approved by (DCI) Drug Controller GENERAL - India For Marketing (Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Itraconazole Antifungal July 1993
Indications- Fungal infections Antifungal- Blastomycosis, Histoplasmosis, Aspergillosis, Onychomycosis Approved by FDA on Sept 11,1992
Dosage: recommended daily dose - 200mg once daily. May be increased in 100mg increments to a maximum of 400mg daily.
Overdosage-
1. Itraconazole is not removed by dialysis.
2. In the event of accidental overdosage, employ supportive neasures, including sodium bicarbonate
Missed dose
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Patient Information:
Refer Ketoconazole
1. Take itraconazole on a full meal.
2. Report any signs and symptoms that may suggest liver dysfunction eg. unusual fatigue, anorexia, nausea, vomiting, jaundice, dark urine or pale stool.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Itraconazole is a potent inhibitor of most human fungal pathogens. It inhibits the synthesis of ergosterol which is the primary celluar sterol in fungi. Inhibition of ergosterol synthesis results in abnormalites of membrane permeability, membrane- bound enzyme activity and coordination of chitin synthesis.
Pharmacokinetics:
Oral bioavailability of itraconazole is 55% because of first pass metabolism. Peak plasma levels after a 100mg dose taken with food have been reported to be 130 to 250mcg/L. Itraconazole is extensively metabolised in the liver. Excretion is through bile and urine, and elimination half-life of intraconazole is 20h.
Interaction with Food:
Absorption of itraconazole was increased when coadministred with a cola beverage with AUC and Cmax increasing 75% and 95% repy.
Pregnancy and lactation:
Pregnancy: Use in pregnancy for systemic fungal infections only if the benefit the hazards.
Lactation: Do not administer to a nursing woman.
Children- Safety and efficacy have not been established
