Actions of Tracon in details
Synthetic broad-spectrum antifungal.
Pharmacology: Tracon, a triazole derivative is active against infections with dermatophytes (Trichophyton and Microsporum spp, Epidermophyton floccosum), yeasts (Cryptococcus neoformans, Pityrosporum sp, Candida sp including C. albicans, C. glabrata and C. krusei), Aspergillus sp, Histoplasma sp, Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea sp, Cladosporium sp, Blastomyces dermatitidis and various other yeasts and fungi.
In vitro studies have demonstrated that Tracon 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.
Pharmacokinetics: Capsule: The oral bioavailability of Tracon is maximal when the capsules are taken immediately after a full meal. Peak plasma levels are reached 3-4 hrs following an oral dose. Elimination from plasma is biphasic with a terminal half-life of 1-1.5 days. During chronic administration, steady state is reached after 1-2 weeks. Steady-state plasma concentrations of Tracon 3-4 hrs after drug intake are 0.4 mcg/mL (100 mg once a day), 1.1 mcg/mL (200 mg once a day) and 2 mcg/mL (200 mg twice a day).
The plasma protein-binding of Tracon is 99.8%. Concentrations of Tracon in whole blood are 60% of those in plasma. Uptake in keratinous tissues, especially the skin, is up to 4 times higher than in plasma, and elimination of Tracon is related to epidermal regeneration. In contrast to the plasma levels which become undetectable within 7 days of stopping therapy, therapeutic levels in the skin persist for 2-4 weeks after discontinuation of a 4-week treatment. Levels of Tracon have been detected in the nail keratin as early as 1 week after start of treatment and persist for at least 6 months after the end of a 3-month course of therapy. Tracon is also present in sebum and to a lesser extent in sweat.
Tracon is also extensively distributed into tissues that are prone to fungal invasion. Concentrations in lung, kidney, liver, bone, stomach, spleen and muscle were found to be 2-3 times higher than the corresponding plasma concentrations.
Therapeutic levels in vaginal tissue are maintained for another 2 days after discontinuation of a 3-day course with 200 mg daily and for another 3 days after discontinuation of a 1-day course with 200 mg twice a day.
Tracon is extensively metabolized by the liver into a large number of metabolites. One of the metabolites is hydroxy-Tracon, which has a comparable antifungal activity in vitro to Tracon. Antifungal drug levels measured by bioassay were about 3 times those of Tracon assayed by high-performance liquid chromatography. Faecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is <0.3% of the dose. About 35% of the dose is excreted as metabolites in the urine within 1 week.
Oral Solution:
The oral bioavailability of Tracon is maximal when Tracon is taken without food. During chronic administration, steady-state is reached after 1-2 weeks. Peak plasma levels are observed 2 hrs (fasting) to 5 hrs (with food) following the oral administration. After repeated once a day administration of Tracon 200 mg in fasting condition, steady-state plasma concentrations of Tracon fluctuate between 1 and 2 mcg/mL (trough to peak). When the oral solution is taken with food, steady-state plasma concentrations of Tracon are about 25% lower.The plasma protein-binding of Tracon is 99.8%. Tracon is extensively distributed into tissues which are prone to fungal invasion. Concentrations in lung, kidney, liver, bone, stomach, spleen and muscle were found to be 2-3 times higher than the corresponding plasma concentrations.
Tracon is extensively metabolized by the liver into a large number of metabolites. One of the metabolites is hydroxy-Tracon which has, in vitro, a comparable antifungal activity to Tracon. Plasma levels of hydroxy-Tracon are about 2 times higher than those of Tracon.
After repeated oral administration, elimination of Tracon from plasma is biphasic with a terminal half-life of 1.5 days. Faecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is <0.03% of the dose. About 35% of the dose is excreted as metabolites in the urine within a week.
How should I take Tracon?
Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.
The Tracon capsule should be taken after a full meal.
Take Tracon oral solution (liquid) on an empty stomach, at least 1 hour before or 2 hours after a meal. Swish the liquid in your mouth for several seconds before swallowing it.
Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.
The Tracon has a special dosing schedule that includes not taking the medicine for several days in a row. Follow all dosing instructions carefully.
Do not crush, chew, break, or open an Tracon capsule. Swallow it whole.
Tracon capsules should not be used in place of Tracon oral solution (liquid) if that is what your doctor has prescribed. Make sure you have received the correct type of this medicine at the pharmacy and ask the pharmacist if you have any questions.
If you also take a stomach acid reducer (Tagamet, Pepcid, Axid, Zantac, and others), take Tracon with an acidic drink such as non-diet cola.
Take this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Tracon will not treat a viral infection such as the common cold or flu.
While using Tracon, you may need frequent blood tests.
Store at room temperature away from moisture, heat, and light.
Tracon administration
Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.
The Tracon capsule should be taken after a full meal.
Take Tracon oral solution (liquid) on an empty stomach, at least 1 hour before or 2 hours after a meal. Swish the liquid in your mouth for several seconds before swallowing it.
Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
Tracon capsules should not be used in place of Tracon oral solution (liquid) if that is what your doctor has prescribed. Make sure you have received the correct type of this medication at the pharmacy and ask the pharmacist if you have any questions.
Take this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Tracon will not treat a viral infection such as the common cold or flu.
While using Tracon, you may need frequent blood tests at your doctor's office.
Store at room temperature away from moisture, heat, and light.
Tracon pharmacology
Pharmacokinetics And Metabolism
General Pharmacokinetic Characteristics
Peak plasma concentrations of Tracon are reached within 2 to 5 hours following oral administration. As a consequence of non-linear pharmacokinetics, Tracon accumulates in plasma during multiple dosing. Steady-state concentrations are generally reached within about 15 days, with Cmax values of 0.5 μg/ml, 1.1 μg/ml and 2.0 μg/ml after oral administration of 100 mg once daily, 200 mg once daily and 200 mg b.i.d., respectively. The terminal half-life of Tracon generally ranges from 16 to 28 hours after single dose and increases to 34 to 42 hours with repeated dosing. Once treatment is stopped, Tracon plasma concentrations decrease to an almost undetectable concentration within 7 to 14 days, depending on the dose and duration of treatment. Tracon mean total plasma clearance following intravenous administration is 278 ml/min. Tracon clearance decreases at higher doses due to saturable hepatic metabolism.
Absorption
Tracon is rapidly absorbed after oral administration. Peak plasma concentrations of Tracon are reached within 2 to 5 hours following an oral capsule dose. The observed absolute oral bioavailability of Tracon is about 55%.
The oral bioavailability of Tracon is maximal when Tracon® (Tracon) Capsules are taken immediately after a full meal. Absorption of Tracon capsules is reduced in subjects with reduced gastric acidity, such as subjects taking medications known as gastric acid secretion suppressors (e.g., H2-receptor antagonists, proton pump inhibitors) or subjects with achlorhydria caused by certain diseases. Absorption of Tracon under fasted conditions in these subjects is increased when Tracon® Capsules are administered with an acidic beverage (such as a non-diet cola). When Tracon® Capsules were administered as a single 200-mg dose under fasted conditions with non-diet cola after ranitidine pretreatment, a H2-receptor antagonist, Tracon absorption was comparable to that observed when Tracon® Capsules were administered alone.
Tracon exposure is lower with the Capsule formulation than with the
Oral Solution when the same dose of drug is given.
Distribution
Most of the Tracon 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 Tracon in plasma is present as free drug. Tracon is distributed in a large apparent volume in the body ( > 700 L), suggesting 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, and the uptake into keratinous tissues, skin in particular, up to four times higher. Concentrations in the cerebrospinal fluid are much lower than in plasma.
Metabolism
Tracon is extensively metabolized by the liver into a large number of metabolites. In vitro studies have shown that CYP3A4 is the major enzyme involved in the metabolism of Tracon. The main metabolite is hydroxy-Tracon, which has in vitro antifungal activity comparable to Tracon; trough plasma concentrations of this metabolite are about twice those of Tracon.
Excretion
Tracon is excreted mainly as inactive metabolites in urine (35%) and in feces (54%) within one week of an oral solution dose. Renal excretion of Tracon and the active metabolite hydroxy-Tracon account for less than 1% of an intravenous dose. Based on an oral radiolabeled dose, fecal excretion of unchanged drug ranges from 3% to 18% of the dose.
As re-distribution of Tracon from keratinous tissues appears to be negligible, elimination of Tracon from these tissues is related to epidermal regeneration. Contrary to plasma, the concentration in skin persists for 2 to 4 weeks after discontinuation of a 4-week treatment and in nail keratin – where Tracon can be detected as early as 1 week after start of treatment – for at least six months after the end of a 3-month treatment period.
Special Populations
Renal Impairment
Limited data are available on the use of oral Tracon in patients with renal impairment. A pharmacokinetic study using a single 200-mg oral dose of Tracon was conducted in three groups of patients with renal impairment (uremia: n=7; hemodialysis: n=7; and continuous ambulatory
Peritoneal dialysis: n=5). In uremic subjects with a mean creatinine clearance of 13 mL/min.
References
- DailyMed. "ITRACONAZOLE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Itraconazole: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Itraconazole: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Tracon are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Tracon. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
3 consumers reported administration
When best can I take Tracon, on an empty stomach, before or after food?ndrugs.com website users have also released a report stating that Tracon should be taken After food. In any case, this may not be the right description on how you ought to take this Tracon. Kindly visit your doctor for more medical advice in this regard. Click here to see other users view on when best the Tracon can be taken.
| Users | % | ||
|---|---|---|---|
| After food | 2 | 66.7% | |
| Empty stomach | 1 | 33.3% | |
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
