Terconazole - Dosage, Indications, and Side Effects

Overview

Terconazole is a broad-spectrum antifungal agent used in the treatment of vulvovaginal candidiasis. The drug contains a triazole ring developed specifically to enhance the antifungal activity. It belongs to a group of drugs called triazoles and is classified as a triazole ketal derivative. Studies have demonstrated that Terconazole is a well-tolerated, highly effective, and fast-acting medication. Terconazole was approved by the United States Food and Drug Administration (US FDA) initially in 1987, and Terconazole vaginal cream was approved on 10th January 2004.

How Does Terconazole Work?

Terconazole is a triazole antifungal drug that was designed to be more specific and active than imidazoles. It acts on the fungal cytochrome P-450, inhibits the growth of yeast organisms (fungi), and destroys them. The drug is stable and less vulnerable to oxidation compared to imidazoles. Studies have revealed that the drug possesses high affinity and selectivity for cytochrome P-450, and Terconazole's spectrum of in vitro activity includes a wide range of pathogenic fungal organisms. This indicates that Terconazole can be highly effective in treating fungal diseases.

Indications of Terconazole:

Terconazole vaginal cream is indicated to treat vulvovaginal candidiasis or vaginal yeast infections.

Contraindications of Terconazole:

Terconazole vaginal cream is contraindicated in patients with known hypersensitivity (an exaggerated response of the immune system) to the drug. There is no data available regarding the cross-hypersensitivity between Terconazole and other antifungal agents of the same group.

Available Doses and Dose Forms

Terconazole is available in the form of 0.4 and 0.8 percent vaginal cream and 80 mg vaginal suppositories. Each gram of vaginal cream contains 8 mg (milligrams) of Terconazole. Each measured dose delivers five grams of Terconazole cream in an applicator containing about 40 mg of the medication. 0.4 percent Terconazole cream must be applied intravaginally once daily for seven days; 0.8 percent cream must be used intravaginally once a day for three days; and vaginal suppositories must be inserted once daily for three days.

Warnings and Precautions

• If the patient experiences fever, chills, irritation, or flu-like symptoms (cough, headache, sore throat, body ache) during the treatment, Terconazole must be discontinued immediately, and the patient must not be retreated with the drug.

• Microbiological studies such as KOH (potassium hydroxide) smear and culture must be performed or repeated to rule out other pathogens in patients who do not respond to treatment with Terconazole.

• Anaphylactic reactions (severe allergic reactions) and toxic epidermal necrolysis (severe skin reactions causing blistering and peeling of the skin) may occur in some patients during the treatment with Terconazole; in such situations, the drug must be discontinued and supportive therapy must be considered.

• Terconazole is a petroleum-based product and can damage the diaphragms or latex (rubber) condoms. Hence, they must be used separately.

Adverse Effects of the Drug

Adverse effects of Terconazole include:

• Fever.

• Abdominal pain.

• Headache.

• Dysmenorrhea (pain during menstruation).

• Itching.

• Burning sensation.

For Patients

What Is Vaginal Yeast Infection?

An infection of the vaginal area caused by a type of fungus (yeast) is called a vaginal yeast infection. It is also called vulvovaginal candidiasis or vaginal candidiasis, as it is often caused by the microorganism known as Candida albicans. It is commonly found in small amounts in the mouth, digestive tract, skin, and vagina (an organ in the female reproductive system), but does not cause any symptoms. However, if there is a rapid growth of Candida organisms above normal, it can cause infections. The normal balance between the microorganisms can vary due to the use of certain medicines during pregnancy, menstruation, hormonal imbalance, diabetes, obesity, or any illness. This infection usually does not spread by sexual contact, but some men may experience symptoms such as itching, irritation, or rash following sexual contact with an infected partner. The symptoms of a vaginal yeast infection include:

• Itching or burning sensation in the vagina.

• Pain during urination.

• Abnormal or thick, white vaginal discharge.

• Redness and swelling of the vaginal area.

• Pain during sexual intercourse.

Medicines are available in the form of creams, suppositories, ointments, and tablets (both oral and vaginal) to manage vaginal yeast infections. A healthcare provider can be consulted before using these medications. Maintaining the genital area clean and dry, avoiding the use of harsh chemicals, douching, tight-fitting clothes, and reducing sugar intake are some of the measures to prevent vaginal yeast infections.

What Is Terconazole?

Terconazole is a prescription medicine used in the treatment of vaginal yeast infections caused by the microorganism Candida albicans. It is an antifungal agent that stops the growth of yeast and reduces symptoms. It is highly effective, fast-acting, and well-tolerated by most patients. Terconazole must be used exactly as prescribed by the healthcare professional or by following the instructions given in the patient leaflet. It must not be discontinued without the doctor’s consent, even if the patient feels better quickly, as the condition may not have been cured completely.

How Effective Is Terconazole?

Terconazole is the first in a new class of antifungal drugs called triazoles. Various studies have demonstrated the safety and effectiveness of both the cream and the suppository in the treatment of vaginal candida infections. The short-term (eight to ten days of therapy) and long-term analyses in the United States also confirmed that the drug was as effective or superior to the other drugs used for the same condition. Terconazole demonstrated an excellent profile in all the studies, with no severe side effects in any treatment regimen.

How Should Terconazole Be Used?

Terconazole must be used exactly as the doctor recommends. Instructions should be followed exactly as given in the leaflet while using the medication.

• Before using Terconazole cream, hands must be washed and dried, and the vaginal area must be cleaned and dried thoroughly. The applicator provided with the product must be filled with the cream or suppository until the plunger stops. The filled applicator is held by the ribbed end of the barrel, and the patient must lie on the back with knees drawn towards the chest. The applicator must be inserted into the vagina as far as comfortable and the plunger must be pressed slowly to release the medication (cream or suppository). The applicator must be removed slowly and washed thoroughly after each use.

• If the suppository is used without the applicator, the tablet must be held on the tip of the finger, and by lying on the back, with knees drawn towards the chest, the suppository must be inserted into the vagina as far as comfortable. Hands must be washed thoroughly before and after each application.

What Are the Side Effects of Terconazole?

Side effects of Terconazole include:

• Fever.

• Chills.

• Headache.

• Pain during menstrual periods.

• Stomach pain.

• Itching or irritation in the vaginal area.

• Burning sensation after cream application.

• Foul-smelling discharge.

What Must the Patient Inform the Doctor Before Taking Terconazole?

• Before starting the treatment, patients must tell the doctor if they are allergic to Terconazole or its ingredients or any other medications.

• Patients must inform the doctor if they are suffering from acquired immunodeficiency syndrome (AIDS), human immunodeficiency virus (HIV) infection, diabetes, or any other immune system disorders before treatment with Terconazole.

• Patients must tell the healthcare professional if they are taking antibiotics, herbal medicines, vitamins or nutritional supplements, over-the-counter (OTC) medications, or other medicines before using Terconazole.

• Patients must inform the doctor if they are pregnant, planning pregnancy, breastfeeding, or if they become pregnant while getting treated with Terconazole.

What Are the Precautionary Measures to Be Followed While Taking Terconazole?

• Terconazole must be used intravaginally and is not for oral use or application to other areas.

• It must be used for three days or exactly as the doctor prescribes, even if the patient feels better quickly.

• If the partner also experiences discomfort, itching, or redness in the genital area, a physician must be consulted immediately.

• Terconazole vaginal cream can be used during menstruation; however, only sanitary pads must be used, as tampons can absorb the medication. An absorbent pantyliner can also be worn while using the drug.

• The vaginal area must not be scratched, as it can increase the irritation or spread the infection.

• Hands must be washed thoroughly with soap and water before and after each application.

• Patients must thoroughly dry the vaginal area after swimming, showering, or after a bath. Damp clothes must be changed immediately, as they can increase the risk of yeast infection.

• The genital area must be wiped from front to back after every bowel movement.

• Douching must not be done, as it may disturb the balance of healthy bacteria or alter pH secretions.

Missed Dose:

The missed dose of Terconazole must be applied or inserted (suppository) as soon as remembered; however, if it is almost time for the next dose, the missed dose can be skipped, and the regular dosing schedule must be followed. A double dose must not be used to compensate for the missed dose.

Storage:

Terconazole vaginal cream and suppositories must be kept at a controlled room temperature of around 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit), away from excess heat and moisture.

For Doctors

Pharmacological Aspects of Terconazole

Mechanism of Action

Terconazole is a broad-spectrum anti-fungal agent against Candida albicans and other fungi by disrupting cell membrane permeability. It inhibits the cytochrome P-450 14 alpha-demethylase enzyme, accumulating lanosterol and other sterols and decreasing the ergosterol concentration. This disturbs the structure and function of the fungal organisms, thus resulting in their destruction. Studies have shown that despite successive passages of Candida albicans, there was no development of resistance to Terconazole.

Pharmacodynamics

Terconazole is a triazole antifungal drug available for intravaginal use. It has three nitrogen molecules in the azole ring and is structurally similar to imidazole-derived antifungal agents. It inhibits 14-alpha-demethylase and ergosterol synthesis in the fungal cell membrane. This disrupts the structure and function of the fungi, leading to its destruction or inhibition of growth.

Pharmacokinetics

• After an intravaginal administration of 0.8 percent Terconazole cream, the absorption rate was 5 to 8 percent in subjects with a history of hysterectomy and 12 to 16 percent in subjects with tubal ligation and without hysterectomy. After daily administration of 0.8 percent Terconazole for seven days in healthy females, the plasma concentration rose to a daily peak at 6.6 hours. Results were similar in studies conducted on female patients with vaginal yeast infections and in pregnant women.

• After an oral administration of 30 mg of radioactive-labeled Terconazole, the mean half-life of elimination from the blood was around 6.9 hours. Terconazole (in vitro) had a high protein-binding rate of 94.9 percent. Terconazole was metabolized extensively; the plasma Area Under the Curve (AUC) for Terconazole compared to the AUC for radioactivity was about 0.6 percent. The total radioactivity was eliminated from the blood with a mean half-life of 52.2 hours.

Drug Interactions

No severe drug interactions were reported with the concomitant use of Terconazole with other drugs, including oral contraceptives.

Clinical Studies

Around 2000 patients with vulvovaginal candidiasis were included in the multicentric studies of intravaginal Terconazole formulations. More basic studies were conducted previously between 1980 and 1982. About 1179 patients were administered vaginal suppositories of 40, 80, and 240 mg and 0.4 and 0.8 percent vaginal cream. Comparative studies of Terconazole with other antimycotics were also conducted on 767 patients. The mycological cure rate received after five treatment schedules was around 90 percent.

Follow-up examinations showed signs of vulvovaginal inflammation in about 10 percent of women. Around 1 to 3 percent of women complained of a transient burning sensation. However, the results confirmed the high antimycotic potential and therapeutic effect of Terconazole, along with the tolerability of all the tested dosage forms.

Nonclinical Toxicology

Carcinogenetic studies have not been conducted with Terconazole. Terconazole was not mutagenic during in vitro Ames tests for induction of microbial point mutations, chromosomal tests, or inducing cellular transformation. Animal studies conducted in female rats with an administration of up to 40 mg/kg/day (milligram per kilogram per day) of Terconazole for three months did not show any significant changes in fertility or the reproductive potential of the rats.

Specific Considerations

• Pregnancy: Adequate and well-controlled clinical trials of Terconazole have not been performed in pregnant women. Therefore, Terconazole vaginal cream is not recommended during pregnancy.

• Lactation: It is not known whether Terconazole is present in breast milk; hence, caution must be exercised when recommending Terconazole to lactating mothers.

• Pediatric Use: The safety and effectiveness of Terconazole have not been established in children and premenarchal females.

• Geriatric Use: A sufficient number of subjects above 65 years of age were not included in the clinical studies of Terconazole to determine their response compared to the younger subjects.