Nextstellis

Last reviewed on RxList: 4/21/2021
Nextstellis Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Nextstellis?

Nextstellis (drospirenone and estetrol tablets) is a combination of the female hormones progestin and estrogen, indicated for use by females of reproductive potential to prevent pregnancy.

What Are Side Effects of Nextstellis?

Side effects of Nextstellis include:

  • irregular vaginal bleeding,
  • mood disturbance,
  • headache,
  • breast enlargement, swelling, pain, tenderness,
  • painful menstrual periods,
  • acne,
  • weight gain, and
  • decreased sex drive

Dosage for Nextstellis

The dose of Nextstellis is one tablet by mouth at the same time every day. Tablets should be taken in the order directed on the blister pack.

Nextstellis In Children

Safety and efficacy of Nextstellis have been established in females of reproductive potential. Use of Nextstellis before menarche is not indicated.

What Drugs, Substances, or Supplements Interact with Nextstellis?

Nextstellis may interact with other medicines such as:

  • strong CYP3A inducers or certain moderate or weak CYP3A inducers,
  • strong CYP3A inhibitors,
  • bile acid sequestrants,
  • anti-diabetic drugs,
  • other drugs that may increase blood potassium levels,
  • lamotrigine,
  • systemic corticosteroids, and
  • thyroid hormone replacement therapy

Tell your doctor all medications and supplements you use.

Nextstellis During Pregnancy and Breastfeeding

Nextstellis is intended to prevent pregnancy and should be discontinued if pregnancy occurs. Nextellis passes into breast milk and may decrease milk production. Breastfeeding women are advised to use other methods of contraception until breastfeeding is discontinued. Consult your doctor before breastfeeding.

Additional Information

Our Nextstellis (drospirenone and estetrol tablets) for Oral Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Which of the following are methods for contraception? See Answer
Nextstellis Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions with the use of COCs are discussed elsewhere in labeling:

  • Serious cardiovascular events including venous and arterial thromboembolism [see BOX WARNING and WARNINGS AND PRECAUTIONS]
  • Hyperkalemia [see WARNINGS AND PRECAUTIONS]
  • Liver disease [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of one drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data provided reflect the experience with the use of NEXTSTELLIS in two large prospective studies, one in Europe/Russia (C301) and one in North America (C302) (N = 3,632) of NEXTSTELLIS for the prevention of pregnancy in females 16-50 years of age. The mean duration of NEXTSTELLIS exposure was 317 and 257 days for the respective studies. The study population was 27 years of age on average, with a mean BMI of 25 kg/m2. The racial distribution was 83% White; 11% Black; 3% Asian; and 3% Other.

Table 4 Adverse Reactions Occurring in ≥ 2% of Females Receiving NEXTSTELLIS in Studies C301 and C302

Preferred Term (PT) Participants with Adverse Reaction – US/Canada Phase 3 trial
(n [%])
(N = 2073)*
Participants with Adverse Reaction – Two Phase 3 trials
(n [%])
(N=3632)**
Any adverse reaction*** 1205 (58.1) 2126 (58.5)
Mood disturbance1 226 (10.9) 329 (9.1)
Bleeding irregularities2 201 (9.7) 393 (10.8)
Breast symptoms3 110 (5.3) 197 (5.4)
Headache4 100 (4.8) 227 (6.3)
Dysmenorrhea5 84 (4.1) 133 (3.7)
Weight increased6 68 (3.3) 108 (3.0)
Acne7 66 (3.2) 136 (3.7)
Libido decreased/lost8 27 (1.3) 72 (2.0)
*Represents the safety population of C302 only (US/Canada).
**Represents the safety population of C301/C302 for DRSP/E4.
***Any adverse reaction equals any adverse event ≥ 2%.
1. Includes PTs: adjustment disorder, affective disorder, agitation, anger, anxiety, depressed mood, depression, depressive symptom, disorientation, emotional disorder, emotional distress, euphoric mood, generalized anxiety disorder, insomnia, irritability, mood altered, mood swings, nervousness, panic attack, panic disorder, performance fear, restlessness, sleep disorder, stress, suicidal ideation, tearfulness
2. Includes PTs: abnormal withdrawal bleeding, amenorrhea, cervix hemorrhage uterine, coital bleeding, dysfunctional uterine bleeding, menometrorrhagia, menorrhagia, menstrual disorder, menstruation irregular, metrorrhagia, oligomenorrhea, polymenorrhea, uterine hemorrhage, vaginal hemorrhage.
3. Includes PTs: anisomastia, breast cyst, breast discoloration, breast discomfort, breast disorder, breast engorgement, breast enlargement, breast mass, breast edema, breast pain, breast swelling, breast tenderness, fibrocystic breast disease, galactorrhea, gynecomastia, mastoptosis, nipple disorder, nipple pain.
4. Includes PTs headache, premenstrual headache, and tension headache.
5. Includes PTs adnexa uteri pain, dysmenorrhea, premenstrual cramps, pelvic discomfort, pelvic pain, uterine spasm.
6. Includes PTs: weight increased, weight fluctuation, body mass index increased, weight loss poor, and obesity.
7. Includes PTs acne and cystic acne.
8. Includes PTs: libido decreased and loss of libido

Adverse Reactions Leading To Study Discontinuation (> 1%)

Of 3,632 females in two clinical studies for prevention of pregnancy in females 16-50 years of age, 9.6% discontinued due to an adverse reaction; the most frequent adverse reaction leading to discontinuation was bleeding irregularity (2.8%). Six subjects (0.17%) discontinued study participation due to new onset of migraine with aura; two subjects (0.05%) discontinued due to severe migraine.

Thromboembolic Disorders And Other Vascular Problems

During studies C301 and C302, one thromboembolic event was reported in a female who had been taking NEXTSTELLIS for 75 days and had normal BMI < 25 kg/m2.

Depression

In Study C302 (US/CA), 36 (1.7%) subjects reported depression while using NEXTSTELLIS. Nine (0.3%) subjects had drug withdrawn as a result of symptoms of depression.

DRUG INTERACTIONS

Effects Of Other Drugs On Hormonal Contraceptives

Clinically significant drug interactions with other drugs that affect NEXTSTELLIS are presented in Table 5.

Table 5. Clinically Significant Drug Interactions With Other Drugs that Affect NEXTSTELLIS

CYP3A Inducers
Clinical Effect DRSP is a CYP3A4 substrate. Concomitant use with strong CYP3A inducers or certain moderate or weak CYP3A inducers may decrease DRSP exposure [see CLINICAL PHARMACOLOGY], which may lead to contraceptive failure.
Prevention or Management Strong CYP3A Inducers Avoid concomitant use. If concomitant use is unavoidable, use an alternative contraceptive method (e.g., intrauterine system) or backup non-hormonal contraceptive method during coadministration and up to 28 days after discontinuation of the strong CYP3A inducer.
Moderate and Weak CYP3A Inducers Use an alternative or backup contraceptive method during coadministration and up to 28 days after discontinuation of the CYP3A inducer, unless the Prescribing Information of the specific moderate or weak CYP3A inducer indicates there is no clinically significant interaction with NEXTSTELLIS.
Strong CYP3A Inhibitors
Clinical Effect DRSP is a CYP3A4 substrate. Concomitant use with a strong CYP3A inhibitor may increase DRSP exposure [see CLINICAL PHARMACOLOGY], which may increase the risk of adverse reactions of NEXTSTELLIS, including hyperglycemia [see WARNINGS AND PRECAUTIONS].
Prevention or Management Consider monitoring serum potassium concentration in patients who take a strong CYP3A4 inhibitor long-term and concomitantly with NEXTSTELLIS.
Drugs that May Reduce the Absorption of NEXTSTELLIS
Clinical Effect Concomitant use with drugs such as bile acid sequestrants may decrease the E4 and DRSP exposure, which may lead to contraceptive failure and/or an increase in breakthrough bleeding.
Prevention or Management Separate time of administration of NEXTSTELLIS and the concomitant drug. Refer to the concomitant drug's Prescribing Information for additional information.

Effects Of NEXTSTELLIS On Other Drugs

Table 6 includes clinically significant drug interactions with NEXTSTELLIS that affect other drugs.

Table 6. Clinically Significant Drug Interactions of NEXTSTELLIS on Other Drugs

Anti-Diabetic Drugs
Clinical Effect Concomitant use of NEXTSTELLIS may reduce the blood glucose lowering effect of anti-diabetic drugs [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Prevention or Management Increase frequency of glucose monitoring and increase anti-diabetic drug dosage, as needed, based on glucose levels.
Drugs that may increase serum potassium concentration
Clinical Effect There is a potential for an increase in serum potassium concentration in females taking NEXTSTELLIS with other drugs that may increase serum potassium concentration [see WARNINGS AND PRECAUTIONS andCLINICAL PHARMACOLOGY].
Prevention or Management Monitor serum potassium concentration in females at increased risk for hyperkalemia.
Lamotrigine
Clinical Effect Concomitant use of NEXTSTELLIS may decrease lamotrigine exposure [see CLINICAL PHARMACOLOGY], which may reduce efficacy of lamotrigine.
Prevention or Management Adjust lamotrigine dosage as recommended in its Prescribing Information based on NEXTSTELLIS initiation or discontinuation.
Systemic Corticosteroids
Clinical Effect Concomitant use of NEXTSTELLIS may increase the exposure of certain systemic corticosteroids, which may increase the risk of corticosteroid-related adverse reactions [see CLINICAL PHARMACOLOGY].
Prevention or Management Follow the recommendation for the corticosteroid in accordance with its Prescribing Information. Consider more frequent monitoring for corticosteroid adverse reactions when used concomitantly with NEXTSTELLIS.
Thyroid Hormone Replacement Therapy
Clinical Effect Concomitant use of NEXTSTELLIS may increase thyroid-binding globulin concentration [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
Prevention or Management Monitor thyroid-stimulating hormone (TSH) level and follow the recommendation for thyroid hormone replacement in accordance with its Prescribing Information.

Read the entire FDA prescribing information for Nextstellis (Drospirenone and Estetrol Tablets)

SLIDESHOW

Choosing Your Birth Control Method See Slideshow

© Nextstellis Patient Information is supplied by Cerner Multum, Inc. and Nextstellis Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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