Haloette

Description

Haloette (etonogestrel and ethinyl estradiol vaginal ring) is a non-biodegradable, flexible, transparent, colorless to almost colorless, combination contraceptive vaginal ring. The active components are etonogestrel (13-ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one) and ethinyl estradiol (19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3,17-diol). Each ring releases on average 0.120 mg/day of etonogestrel and 0.015 mg/day of ethinyl estradiol over a three-week period of use. Haloette is composed of ethylene vinylacetate copolymers (28% and 9% vinylacetate) and magnesium stearate. The total content of the active ingredients in each ring is 11.7 mg etonogestrel and 2.7 mg ethinyl estradiol. Haloette is not made with natural rubber latex. The ring has an outer diameter of 54 mm and a cross-sectional diameter of 4 mm. The molecular weights for etonogestrel and ethinyl estradiol are 324.46 and 296.40, respectively.

Uses and Indications

Haloette is an estrogen/progestin combination hormonal contraceptive (CHC) indicated for use by women to prevent pregnancy. This product is specifically intended to prevent pregnancy and does not provide protection against HIV infection (AIDS) or other sexually transmitted diseases.

There are no teratogenic or nonteratogenic effects associated with this drug.

Dosage and Administration

One Haloette should be inserted into the vagina. The ring must remain in place continuously for a duration of three weeks. Following this period, a one-week ring-free interval is required. It is essential that the ring is not removed during the three-week usage period to ensure optimal efficacy.

Contraindications

Use of Haloette is contraindicated in the following situations:

Patients with a high risk of arterial or venous thrombotic diseases due to the potential for exacerbation of these conditions.

Individuals with breast cancer, as the product may promote tumor growth.

Patients with liver tumors or liver disease, given the risk of hepatic complications.

Those experiencing undiagnosed abnormal uterine bleeding, as this may mask underlying conditions.

Pregnant individuals, due to potential harm to the fetus.

Patients with hypersensitivity to any components of Haloette, including a history of anaphylaxis or angioedema.

Co-administration with Hepatitis C drug combinations containing ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, is contraindicated due to the risk of significant drug interactions.

Warnings and Precautions

Cigarette smoking significantly increases the risk of serious cardiovascular events associated with the use of combination hormonal contraceptives (CHCs). Therefore, women over the age of 35 who smoke are advised against the use of Haloette.

In terms of general precautions, it is imperative to discontinue Haloette immediately if a thrombotic event occurs. Additionally, the use of Haloette should be halted at least four weeks prior to and maintained through two weeks after any major surgical procedure. For women who are not breastfeeding, initiation of Haloette should not occur earlier than four weeks postpartum.

Healthcare professionals should be vigilant for signs of Toxic Shock Syndrome (TSS). If a patient presents with symptoms indicative of TSS, it is crucial to consider this diagnosis and initiate appropriate medical evaluation and treatment promptly.

Patients with liver disease should discontinue Haloette if jaundice develops. For women with well-controlled hypertension, regular monitoring of blood pressure is essential; if there is a significant increase in blood pressure, Haloette should be stopped.

Monitoring is also recommended for prediabetic and diabetic women, as Haloette may affect carbohydrate and lipid metabolism. For those with uncontrolled dyslipidemia, an alternative contraceptive method should be considered.

Any significant changes in headache patterns should be evaluated, and Haloette should be discontinued if warranted. Irregular uterine bleeding or amenorrhea should also be assessed to determine the appropriate course of action.

Laboratory tests should include monitoring for prediabetic and diabetic women to ensure safe use of Haloette.

In cases where patients exhibit signs or symptoms of TSS, immediate medical evaluation and treatment are necessary. Furthermore, healthcare providers should instruct patients to stop using Haloette and contact their doctor if any of the following occur: a thrombotic event, development of jaundice, significant increases in blood pressure, or notable changes in headache patterns.

Side Effects

Patients using Haloette may experience a range of adverse reactions, which can be categorized by frequency and seriousness.

Common adverse reactions occurring in 2% or more of patients include vaginitis (13.8%), headache (including migraine) (11.2%), and mood changes such as depression and mood swings (6.4%). Other frequently reported reactions are device-related events (6.3%), nausea/vomiting (5.9%), vaginal discharge (5.7%), and increased weight (4.9%). Additional common reactions include vaginal discomfort (4.0%), breast pain or tenderness (3.8%), dysmenorrhea (3.5%), abdominal pain (3.2%), acne (2.4%), and decreased libido (2.0%).

Certain adverse reactions have led to study discontinuation in 1% or more of participants, including device-related events (2.7%), mood changes (1.7%), headache (1.5%), and vaginal symptoms (1.2%).

Serious adverse reactions reported include deep vein thrombosis, anxiety, cholelithiasis, and vomiting. Postmarketing experience has revealed additional serious events such as stroke or cerebrovascular accident, arterial events (including arterial thromboembolism and myocardial infarction), and hypersensitivity reactions, including anaphylaxis and angioedema. Other notable postmarketing reactions include aggravation of varicose veins, urticaria, chloasma, penile disorders in male partners, and galactorrhea. Device breakage has also been reported, particularly with the concomitant use of intravaginal antimycotic, antibiotic, and lubricant products, as well as vaginal injury associated with ring breakage.

Warnings associated with Haloette usage include an increased risk of serious cardiovascular events in women who smoke, particularly those over 35 years of age. It is advised that these women refrain from using Haloette. Additionally, if patients exhibit signs or symptoms of Toxic Shock Syndrome (TSS), appropriate medical evaluation and treatment should be initiated. Discontinuation of Haloette is recommended if jaundice develops, if there is a significant rise in blood pressure in women with well-controlled hypertension, or if there are significant changes in headache patterns. Monitoring is advised for prediabetic and diabetic women, and alternate contraceptive methods should be considered for those with uncontrolled dyslipidemia. Irregular bleeding or amenorrhea should also be evaluated.

Drug Interactions

Drugs or herbal products that induce enzymes, particularly CYP3A4, may reduce the effectiveness of combined hormonal contraceptives (CHCs) and potentially lead to increased breakthrough bleeding. It is advised that patients using CHCs concurrently with enzyme inducers be counseled to employ a backup or alternative method of contraception to ensure adequate contraceptive efficacy.

No specific drug and laboratory test interactions have been identified.

Packaging & NDC

The table below lists all NDC Code configurations of Haloette (etonogestrel and ethinyl estradiol), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and efficacy of Haloette have been established in women of reproductive age. Efficacy is expected to be comparable for postpubertal adolescents under the age of 18 and for users 18 years and older. However, the use of this product is not indicated for individuals before menarche.

Geriatric Use

Elderly patients, specifically those who are postmenopausal, have not been included in clinical studies of Haloette. As such, the safety and efficacy of this medication in this demographic remain undetermined. Therefore, Haloette is not indicated for use in postmenopausal women. Healthcare providers should exercise caution when considering treatment options for elderly patients, particularly those who fall within this category, and should explore alternative therapies that have been adequately studied in this population.

Pregnancy

Haloette is contraindicated during pregnancy, as there is no need for pregnancy prevention in women who are already pregnant. Epidemiologic studies and meta-analyses have not demonstrated an increased risk of genital or non-genital birth defects, including cardiac anomalies and limb-reduction defects, following maternal exposure to low-dose combined hormonal contraceptives (CHCs) prior to conception or during early pregnancy.

Animal studies have shown that no adverse developmental outcomes were observed in pregnant rats and rabbits when etonogestrel was administered during organogenesis at doses approximately 300 times the anticipated daily vaginal human dose (~0.002 mg/kg/day). Similarly, the co-administration of desogestrel and ethinyl estradiol during organogenesis did not result in adverse developmental outcomes at doses at least 2/5 times the anticipated daily vaginal human dose.

However, caution is warranted as the co-administration of a maternally toxic dose of desogestrel/ethinyl estradiol to pregnant rats was associated with embryolethality and wavy ribs at doses that were 40/130 times the anticipated vaginal human dose. In contrast, no adverse embryofetal effects were observed when the combination was administered to pregnant rats at doses that were 4/13 times the anticipated vaginal human dose. In pregnant rabbits, preimplantation loss was noted at a desogestrel/ethinyl estradiol dose that was 3/10 times the anticipated vaginal human dose, while no adverse effects were observed at doses that were 2/5 times the anticipated vaginal human dose.

Healthcare professionals should discontinue the use of Haloette if pregnancy is confirmed.

Lactation

Small amounts of contraceptive steroids and/or metabolites, including etonogestrel and ethinyl estradiol, are transferred to human milk. However, harmful effects have not been observed in breastfed infants exposed to combined hormonal contraceptives (CHCs) through breast milk.

It is important to note that CHCs can reduce milk production in breastfeeding mothers. This reduction is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Therefore, when possible, it is advisable to recommend that nursing mothers use non-estrogen-containing contraception until they have completely weaned their child.

The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for Haloette and any potential adverse effects on the breastfed child from Haloette or from the underlying maternal condition.

Renal Impairment

The effect of renal impairment on the pharmacokinetics of Haloette has not been studied. Therefore, dosing adjustments, monitoring, or specific precautions for patients with reduced renal function cannot be established. Healthcare professionals should exercise caution when prescribing Haloette to patients with renal impairment, as the lack of data necessitates careful consideration of potential risks and benefits.

Hepatic Impairment

Patients with hepatic impairment may experience altered pharmacokinetics of Haloette, although the specific effects have not been studied. It is important to note that steroid hormones may be poorly metabolized in individuals with compromised liver function.

In cases of acute or chronic disturbances of liver function, the use of combined hormonal contraceptives (CHCs) such as Haloette may need to be discontinued until liver function markers return to normal. Additionally, if jaundice develops, Haloette should be discontinued immediately.

Healthcare providers should closely monitor liver function in patients with hepatic impairment and make appropriate clinical decisions regarding the use of Haloette based on the patient's liver health.

Overdosage

Overdosage may lead to withdrawal bleeding in females, as well as nausea. In the event of a suspected overdose, it is imperative that all Haloette rings be removed immediately. Following the removal, symptomatic treatment should be administered as necessary to address any adverse effects.

It is noteworthy that there have been no reported cases of serious ill effects resulting from an overdose of combined hormonal contraceptives (CHCs). This suggests a relatively favorable safety profile in the context of overdosage, although monitoring and appropriate management remain essential.

Nonclinical Toxicology

In a 24-month carcinogenicity study conducted in rats with subdermal implants releasing 10 and 20 mcg of etonogestrel per day, which corresponds to approximately 0.3 and 0.6 times the systemic steady-state exposure observed in women using the etonogestrel and ethinyl estradiol vaginal ring, no drug-related carcinogenic potential was identified.

Etonogestrel was evaluated for mutagenic potential and was found to be non-genotoxic in several assays, including the in vitro Ames/Salmonella reverse mutation assay, the chromosomal aberration assay in Chinese hamster ovary cells, and the in vivo mouse micronucleus test.

A fertility study involving etonogestrel was performed in rats at a dose approximately 600 times the anticipated daily vaginal human dose (approximately 0.002 mg/kg/day). The results indicated that treatment did not adversely affect litter parameters following the cessation of treatment, thereby supporting the conclusion that fertility was restored after suppression with etonogestrel.

Postmarketing Experience

During post-approval use of etonogestrel and ethinyl estradiol vaginal ring, the following adverse reactions have been reported voluntarily or through surveillance programs. Due to the nature of voluntary reporting from a population of uncertain size, it is not always feasible to reliably estimate the frequency of these events or establish a causal relationship to drug exposure.

Immune System Disorders Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported.

Nervous System Disorders Cases of stroke and cerebrovascular accidents have been identified.

Vascular Disorders Reports of arterial events, including arterial thromboembolism and myocardial infarction, as well as aggravation of varicose veins, have been noted.

Skin and Subcutaneous Tissue Disorders Instances of urticaria and chloasma have been documented.

Reproductive System and Breast Disorders Penile disorders, including local reactions on the penis in male partners of women using the vaginal ring, and cases of galactorrhea have been observed.

General Disorders and Administration Site Conditions Device breakage has been reported, including instances occurring with the concomitant use of intravaginal antimycotic, antibiotic, and lubricant products.

Injury, Poisoning and Procedural Complications Vaginal injury, along with associated pain, discomfort, and bleeding, has been reported in connection with ring breakage.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. Healthcare providers should counsel patients regarding the increased risk of cardiovascular events associated with the use of Haloette. It is important to inform patients that cigarette smoking significantly elevates the risk of serious cardiovascular events when using Haloette, particularly for women over 35 years old who smoke, as they should not use this product.

Patients should be made aware that the risk of venous thromboembolism (VTE) is heightened compared to non-users of combined hormonal contraceptives (CHCs), especially during the initial use or after a break of four weeks or more from using the same or a different CHC. Additionally, it should be communicated that Haloette does not provide protection against HIV infection (AIDS) or other sexually transmitted infections.

Healthcare providers should instruct patients on the proper usage of Haloette, including what actions to take if they do not adhere to the recommended timing for insertion and removal. Patients should be advised to regularly check for the presence of Haloette in the vagina, particularly before and after intercourse.

It is crucial to inform patients that Haloette is contraindicated during pregnancy. If a patient plans to become pregnant or discovers she is pregnant while using Haloette, she should discontinue its use immediately. Furthermore, patients need to be instructed to use a barrier method of contraception if the ring is out for more than three continuous hours until Haloette has been used continuously for at least seven days.

Patients should also be advised to utilize a backup or alternative method of contraception when taking enzyme inducers alongside Haloette. For those who start using Haloette postpartum and have not yet experienced a normal menstrual period, it is important to recommend the use of an additional non-hormonal method of contraception for the first seven days.

Healthcare providers should inform patients that the use of combined hormonal contraceptives may reduce breast milk production, although this is less likely if breastfeeding is well established. Patients should be made aware that amenorrhea may occur and that pregnancy should be ruled out in cases of amenorrhea if Haloette has been out of the vagina for more than three consecutive hours, if the ring-free interval has been extended beyond one week, if the patient has missed a period for two or more consecutive cycles, or if the ring has been retained for longer than four weeks.

Finally, patients should receive guidance on the proper disposal of a used Haloette to ensure safe and responsible handling.

Storage and Handling

Haloette is supplied in a reclosable sachet, which should be stored refrigerated at a temperature of 2-8°C (36-46°F) prior to dispensing to the user. Once dispensed, Haloette can be stored for up to 6 months at a controlled room temperature of 25°C (77°F), with permissible excursions between 15-30°C (59-86°F).

It is essential to avoid exposure to direct sunlight and to refrain from storing Haloette at temperatures exceeding 30°C (86°F). After use, the ring should be placed back into the reclosable sachet and disposed of in a waste receptacle that is out of reach of children and pets. Haloette should not be flushed down the toilet.

Additional Clinical Information

Five studies evaluating the association between combined oral contraceptive (COC) use and breast cancer risk have shown no significant correlation between ever-use (current or past) of COCs and breast cancer, with effect estimates ranging from 0.90 to 1.12. In contrast, three studies comparing current or recent COC users (defined as less than six months since last use) to never users indicated a varied risk profile. One study found no association, while the other two reported an increased relative risk of breast cancer, ranging from 1.19 to 1.33. Notably, these studies indicated that the risk of breast cancer increased with the duration of current use, with relative risks from 1.03 for less than one year of use to approximately 1.4 for more than 8-10 years.

Adverse reactions identified during post-approval use include a range of disorders. Immune system disorders such as hypersensitivity reactions, including anaphylaxis and angioedema, have been reported. Neurological events, including stroke and cerebrovascular accidents, as well as vascular disorders like arterial thromboembolism and myocardial infarction, have also been noted. Skin reactions such as urticaria and chloasma, reproductive system issues including penile disorders in male partners, and galactorrhea have been documented. Additionally, general disorders related to device use, such as breakage when used with certain intravaginal products, and complications like vaginal injury associated with ring breakage, have been observed.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Haloette as submitted by Dr. Reddy's Labratories Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)