Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Ortho-McNeil Pharmaceutical, Inc.
Terconazole is an Antifungal agent belonging to the pharmacological class of Imidazole Antifungals.
Terconazole has been approved to relieve symptoms and also for the treatment and maintenance of Vulvovaginal candidiasis
After intravaginal administration in humans, terconazole is absorbed at a rate of 5-8% in hysterectomized subjects and 12-16% in non-hysterectomized subjects with tubal ligations. The drug demonstrates a high protein binding of approximately 94.9%. Once systemically absorbed, terconazole undergoes rapid and extensive metabolism through pathways like oxidatative N- and O-dealkylation, dioxolane ring cleavage, and conjugation. Regarding elimination, after 30 mg of orally administered 14C-labelled terconazole, the drug is excreted through both renal (32-56%) and fecal (47-52%) routes. However, specific information on the volume of distribution is not available.
The common side effects of Terconazole include Vaginal irritation or burning, Itching or rash in the vaginal area, Abdominal pain or discomfort, Headache, Nausea or vomiting, Unpleasant taste in the mouth, Dizziness or lightheadedness.
Terconazole is available in the form of Vaginal cream , Suppository.
Terconazole is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.
Terconazole, belonging to the pharmacological class of Imidazole Antifungal, acts as an Antifungal agent.
Terconazole's antifungal activity is believed to be achieved by disrupting the normal permeability of the fungal cell membrane. It, along with other triazole antifungal agents, inhibits cytochrome P450 14-alpha-demethylase in susceptible fungi. This inhibition results in the accumulation of lanosterol and other methylated sterols, leading to a reduction in the concentration of ergosterol in the fungal cell membrane. The depletion of ergosterol disrupts the structure and function of the fungal cell, ultimately leading to a decrease or inhibition of fungal growth.
Terconazole has been approved to relieve symptoms and also for the treatment and maintenance of Vulvovaginal candidiasis.
Terconazole is found to be available in the form of Vaginal cream , Suppository.
Terconazole can be used in the following treatment:
- Vulvovaginal candidiasis
Terconazole can help to relieve symptoms and also for the treatment and maintenance of Vulvovaginal candidiasis .
Terconazole is approved for use in the following clinical indications:
- Vulvovaginal candidiasis
- Vulvovaginal candidiasis: Terconazole has demonstrated effectiveness as a single-dose treatment for vulvovaginal candidiasis. To administer, insert one full applicator intravaginally using the prefilled applicator provided. It is advisable to consider administering Terconazole just before bedtime, which may be a preferred time for treatment.
Terconazole is available in the following dosage forms and strengths:
- Vaginl Cream: 0.4% and 0.8%
- Suppository 80mg
Vaginal cream, Suppository.
- Dosage Adjustments in Kidney Patients:
There are found to be no dosage adjustments in the manufacturer's labeling.
- Dosage Adjustments in Hepatic Impairment Patients:
There are found to be no dosage adjustments in the manufacturer's labeling.
- Dosage Adjustments in Pediatric Patients:
No dosage adjustments in pediatric patients has been included in the product monograph.
When taking Terconazole, there are certain dietary restrictions that should be followed to ensure the medication's effectiveness and safety:
- There are no specific food warnings associated with the use of Terconazole. It is a topical antifungal agent meant for external use on the skin. Since it is not ingested or absorbed systemically, there is generally no interaction with food.
The dietary restriction should be individualized as per patient requirements.
Terconazole may be contraindicated under the following conditions:
Hypersensitivity to the active substance or to any of the excipientsWARNINGS
There are no specific warnings associated with terconazole use.
PRECAUTIONS
General: If sensitization, irritation, fever, chills, or flu-like symptoms are reported during the use of terconazole, discontinue use and do not retreat with the medication.
The base present in the suppository formulation may interact with certain rubber or latex products, such as those used in vaginal contraceptive diaphragms. Therefore, concurrent use of terconazole with such products is not recommended.
Breast Feeding Warning
The excretion of this drug in human milk is not known. Animal studies have indicated that rat offspring exposed to the milk of treated dams showed decreased survival during the early post-partum days, but their overall weight and weight gain were similar to or higher than controls throughout lactation (40 mg/kg/orally). Given that many drugs are excreted in human milk and considering the potential for adverse reactions in nursing infants from terconazole, a decision should be made after considering the drug's importance to the mother, whether to discontinue nursing or discontinue the drug.
Pregnancy Warning
Pregnancy:
Pregnancy Category C.
Studies conducted in rats and rabbits did not show any evidence of teratogenicity when terconazole was orally administered up to 40 mg/kg/day in rats (25 times the recommended intravaginal human dose of the suppository formulation, 50 times the recommended intravaginal human dose of the 0.8% vaginal cream formulation, and 100 times the intravaginal human dose of the 0.4% vaginal cream formulation), up to 20 mg/kg/day subcutaneously in rats, or up to 20 mg/kg/day in rabbits.
Dosages at or below 10 mg/kg/day did not result in embryotoxicity, although a delay in fetal ossification was observed at 10 mg/kg/day in rats. At higher doses (20-40 mg/kg), some evidence of embryotoxicity was found in rabbits and rats. In rats, this was characterized by a decrease in litter size, a reduced number of viable young, and a decrease in fetal weight. Additionally, a delay in ossification and an increased incidence of skeletal variants were noted.
The no-effect dose of 10 mg/kg/day in pregnant rats led to a mean peak plasma level of terconazole of 0.176 mcg/mL, which is significantly higher than the mean peak plasma levels observed in normal subjects after intravaginal administration of terconazole in various formulations (0.004 mcg/mL for terconazole 0.4% vaginal cream, 0.006 mcg/mL for terconazole 0.8% vaginal cream, and 0.010 mcg/mL for terconazole 80 mg vaginal suppository). However, this safety assessment does not consider the potential direct transfer of terconazole to the fetus through diffusion across amniotic membranes from an irritated vagina.
Considering that terconazole is absorbed from the human vagina, its use in the first trimester of pregnancy should be avoided unless the physician deems it essential for the patient's well-being.
Food Warning
There are certain food-related warnings and precautions to consider when using Terconazole:
- There are no specific food warnings associated with the use of Terconazole. It is a topical antifungal agent meant for external use on the skin. Since it is not ingested or absorbed systemically, there is generally no interaction with food.
The adverse reactions related to Terconazole can be categorized as follows:
Common:
● Vaginal irritation or burning
● Itching or rash in the vaginal area
● Abdominal pain or discomfort
● Headache
● Nausea or vomiting
● Unpleasant taste in the mouth
Less Common:
● Diarrhea
The following are the side effects involving Terconazole:
● Vaginal irritation or burning
● Itching or rash in the vaginal area
● Abdominal pain or discomfort
● Headache
● Nausea or vomiting
● Unpleasant taste in the mouth
● Dizziness or lightheadedness
The use of Terconazole should be prudent in the following group of special populations:
Pregnancy:
Pregnancy Category C.
Studies conducted in rats and rabbits did not show any evidence of teratogenicity when terconazole was orally administered up to 40 mg/kg/day in rats (25 times the recommended intravaginal human dose of the suppository formulation, 50 times the recommended intravaginal human dose of the 0.8% vaginal cream formulation, and 100 times the intravaginal human dose of the 0.4% vaginal cream formulation), up to 20 mg/kg/day subcutaneously in rats, or up to 20 mg/kg/day in rabbits.
Dosages at or below 10 mg/kg/day did not result in embryotoxicity, although a delay in fetal ossification was observed at 10 mg/kg/day in rats. At higher doses (20-40 mg/kg), some evidence of embryotoxicity was found in rabbits and rats. In rats, this was characterized by a decrease in litter size, a reduced number of viable young, and a decrease in fetal weight. Additionally, a delay in ossification and an increased incidence of skeletal variants were noted.
The no-effect dose of 10 mg/kg/day in pregnant rats led to a mean peak plasma level of terconazole of 0.176 mcg/mL, which is significantly higher than the mean peak plasma levels observed in normal subjects after intravaginal administration of terconazole in various formulations (0.004 mcg/mL for terconazole 0.4% vaginal cream, 0.006 mcg/mL for terconazole 0.8% vaginal cream, and 0.010 mcg/mL for terconazole 80 mg vaginal suppository). However, this safety assessment does not consider the potential direct transfer of terconazole to the fetus through diffusion across amniotic membranes from an irritated vagina.
Considering that terconazole is absorbed from the human vagina, its use in the first trimester of pregnancy should be avoided unless the physician deems it essential for the patient's well-being.
Lactation
The excretion of this drug in human milk is not known. Animal studies have indicated that rat offspring exposed to the milk of treated dams showed decreased survival during the early post-partum days, but their overall weight and weight gain were similar to or higher than controls throughout lactation (40 mg/kg/orally). Given that many drugs are excreted in human milk and considering the potential for adverse reactions in nursing infants from terconazole, a decision should be made after considering the drug's importance to the mother, whether to discontinue nursing or discontinue the drug.
Pediatric:
The safety and efficacy of this product have not been demonstrated in children.
Geriatric Use:
Clinical trials of Terconazole did not involve an adequate number of participants aged 65 and older, preventing the determination of potential differences in their response compared to younger subjects. However, based on other clinical observations, there have been no reported differences in responses between elderly and younger patients.
The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Terconazole.
To date, there have been no reports of overdose with terconazole in humans. In rat studies, the oral LD50 values were determined to be 1741 mg/kg for males and 849 mg/kg for females. For dogs, the oral LD50 values were approximately 1280 mg/kg for males and at least 640 mg/kg for females.
If someone accidentally ingests Terconazole® 7 vaginal cream orally, it is important to implement supportive and symptomatic measures. In case of accidental application of the cream to the eyes, promptly rinse the eyes with clean water or saline.
Pharmacodynamics:
Terconazole, an intravaginally used triazole antifungal agent, is structurally associated with imidazole-derived antifungal agents. Unlike imidazoles, terconazole and other triazoles feature an azole ring with three nitrogen atoms. By targeting and inhibiting the 14-alpha-demethylase (lanosterol 14-alpha-demethylase), terconazole disrupts the synthesis of ergosterol in fungal membranes. This depletion of ergosterol leads to significant structural and functional disruptions, ultimately inhibiting fungal growth.
Pharmacokinetics:
Absorption
● Vaginal Retention: The majority of terconazole applied intravaginally (mean >60%) remains localized in the vaginal area.
● Limited Systemic Absorption: The absorption of terconazole into the systemic circulation is slow and limited, accounting for less than 20% of the applied dose.
● Time to Peak Concentration: The cream application leads to maximum plasma concentrations of terconazole occurring approximately 5 to 10 hours later.
● Dose-Proportional Systemic Exposure: The systemic exposure to terconazole is directly related to the dose applied, with proportional increases observed.
● Consistent Absorption: Absorption rates and extents of terconazole are similar in both patients with vulvovaginal candidiasis (pregnant or non-pregnant) and healthy subjects.
Distribution
● High Protein Binding: Terconazole exhibits significant protein binding, with approximately 94.9% of the drug bound to proteins.
● Concentration-Independent Binding: The degree of protein binding remains consistent regardless of the drug concentration.
Metabolism
● Extensive Metabolism: Once systemically absorbed, terconazole undergoes substantial metabolism (>95%).
Elimination
● Plasma Elimination Half-Life: Across various studies, the mean elimination half-life of unchanged terconazole from plasma ranges from 6.4 to 8.5 hours.
● Routes of Excretion: Following intravaginal administration, elimination of terconazole from the systemic circulation occurs through both renal (3 to 10%) and fecal (2 to 6%) routes.
- Workowski KA et al. published the sexually transmitted infections treatment guidelines in 2021 (MMWR Recomm Rep. 2021;70(4):1-187. doi:10.15585/mmwr.rr7004a1 [PubMed 34292926]).
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