Zuranolone - Hope for Postpartum Well-Being and Revitalizing Joy

Overview:

Zuranolone is an oral medication prescribed for the treatment of postpartum depression. Postpartum depression is known for the depression that occurs right after childbirth. This drug received its Food and Drug Administration (FDA) approval for its medical use for the treatment of postpartum depression in adults in the United States in August 2023.

Zuranolone is the very first and only oral treatment approved for females with postpartum depression. This drug is also under the development process for its use in the treatment of major depressive disorder (a mental health disorder characterized by a minimum of two weeks of low mood, loss of interest, and low self-esteem). However, the application for such use was limited due to the inadequate evidence of effectiveness.

Drug Group:

Zuranolone is an orally active and inhibitory pregnant neurosteroid. It shows positive allosteric modulation with the gamma-aminobutyric acid and GABA (A) receptors.

Available Doses and Dosage Forms:

Zuranolone comes in oral capsules. It is recommended to take Zuranolone medication orally. The three distinctive strengths of Zuranolone include the following:

• 20 milligrams.

• 25 milligrams.

• 30 milligrams.

For Patients:

What Is Postpartum Depression?

Postpartum depression refers to the depression occurring in women after childbirth. People with postpartum depression carry a higher risk of developing major depression in their later life. Postpartum depression tends to affect nearly 15 percent of people. Women with such depression encounter physical, mental, emotional, and social changes after the delivery. The symptoms of postpartum depression range from mild to severe, occurring within a week of childbirth or sometimes at gradual degrees. The symptoms can last for several days to months. One could experience the following:

• High and low moods.

• Frequent crying.

• Fatigue.

• Irritability.

• Guilt.

• Anxiety.

• Inability to cry.

How Does Zuranolone Work?

Postpartum depression is effectively treated with antidepressant medications and psychotherapy. Zuranolone is a neuroactive steroid used for treating postpartum depression in adults. It works by rebalancing and restoring the brain systems that are responsible for functions, including behavior, mood, thoughts, arousal, and cognition. It shows a positive effect on GABA receptors. Depression and certain mental health conditions are known to occur as a result of an imbalance in GABA.

What Is the Dosage of Zuranolone?

Zuranolone is available in capsule form with 20 mg, 25 mg, and 30 mg dosages. Zuranolone is advised to be taken once a day in the evening, with fatty food items, for two weeks (14 days). The dosage of Zuranolone for postpartum depression is 50 milligrams once daily for 14 days. However, the dosage can be sometimes reduced to 40 mg. This medication can be given alone as a single treatment or given in conjugation with other oral antidepressant tablets.

What Are the Things to Inform the Doctor Before Taking the Drug?

• Inform the doctors if one has an allergy to Zuranolone or any other ingredients of the prescribed formulation.

• Tell the healthcare professionals about the medical conditions one has or ever had in the past.

• Be certain to inform the doctor if one has or ever had any liver or kidney problems.

• Inform the doctors about all the medications one takes. This includes prescription drugs, over-the-counter medicines, vitamins, nutritional supplements, and herbal products.

• Be sure to mention pharmaceutical drugs like antidepressants, central nervous system (CNS) depressants, and opioids if one takes them.

• Additionally, the doctor should know if one has a habit of alcohol consumption and drug use. Inform the doctor if one has been abused or dependent on alcohol, medicines, substances, and drugs.

• Inform the doctors if one is pregnant or has any plans for pregnancy. Zuranolone might harm the unborn baby.

• Inform the doctor if one breastfeeds or plans to do so. Zuranolone is known to pass into the breast milk. But, it is still not known whether it harms the infant. Discuss with the healthcare providers regarding the potential benefits and risks of breastfeeding during Zuranolone therapy.

Women who can become pregnant should consider the following things since Zuranolone is known to harm the fetus when taken during pregnancy.

• Firstly, inform the doctors if one becomes pregnant or plans to be conceived during treatment with Zuranolone.

• Call and inform the doctor if one abruptly becomes pregnant during the treatment course.

• One must use effective birth control aids during Zuranolone therapy and for about one week following the final dosage.

How Is Zuranolone Administered?

• One must take the medication as per the doctor’s prescription and manufacturer’s label information.

• Take the Zuranolone capsule once daily in the evening time with a good fat-containing food item.

• The doctors recommend the type of food items one must take with the medication.

• The doctors might adjust the dosage according to the conditions and suspected side effects.

• Nevertheless, one should not change the dosage or stop the treatment without the doctor’s consent.

• Report to the doctor promptly if one experiences any undesirable reactions.

What Are the Side Effects of Zuranolone?

Zuranolone is regarded as a safe and effective drug for treating postpartum depression in women. But it can even cause certain unwanted reactions. The common side effects of the drug Zuranolone include the following. One should inform the doctor right away if these effects are distressing,

• Dizziness.

• Diarrhea.

• Common cold.

• Tiredness.

• Sleepiness.

• Drowsiness.

• Urinary tract infections.

• Muscle pain.

Serious Side Effects and Considerations:

Zuranolone might cause serious side effects in some instances. These include:

• Decreased Driving Ability: Zuranolone might interfere with one’s alertness and awareness, affecting the ability to drive the vehicle safely. It can also influence the safety of doing certain potentially hazardous activities. One should not drive, work machinery, or do dangerous acts for a minimum of 12 hours after every dose of Zuranolone during the complete treatment course.

• CNS Depressant Effects: Zuranolone can cause central nervous system (CNS) depressant effects like sleepiness, confusion, dizziness, gradual thinking, difficulty walking, and drowsiness.

• One can be at higher risk of falls due to the aforementioned symptoms.

• Taking alcohol can even worsen the symptoms, resulting in trouble breathing. So, one should not take alcohol during Zuranolone therapy.

• One should inform the doctor of experiencing any of these symptoms or if they worsen during the treatment. The doctors might recommend either to stop or decrease the dosage.

• Suicidal Thoughts: Zuranolone might increase the risk of suicidal thoughts and behaviors, particularly when used with other CNS depressants. So it is crucial to look for the changes to prevent such thoughts.

• One must concentrate on the mental health changes, including abrupt changes in mood, thoughts, conduct, and feelings.

• Inform the doctor if any change is suspected in moods and behaviors.

Dietary Considerations:

One can follow the routine classic diet plan until the doctors utter any changes or restrictions. However, one should follow a well-balanced diet to have sound health. The doctors advise one to take really good fat-containing food items. Also, it is advised to avoid alcohol during the treatment of Zuranolone.

Missed Dose:

If one forgets to take the dosage, then skip the missed dose and take the subsequent one at the regular frequency (the next evening). One should not take two capsules of Zuranolone to compensate for the missed dose. Moreover, one should continue taking the tablet once daily until the remaining treatment course (14 days) is completed.

Overdose:

If one takes too much of the drug Zuranolone, it is essential to seek a healthcare provider right away. So reach out to the medical help or poison control helpline if one overdoses with Zuranolone.

Storage

Store the Zuranolone medication at room temperature of 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit), keeping away from heat, moisture, and light. The excursion can be allowed between 15 and 30 degrees Celsius (59 to 86 degrees Fahrenheit). These medications should be kept away from the reach of little ones.

For Doctors:

Clinical Data of Zuranolone:

Drug Name: Zuranolone.

Generic Name: Zuranolone.

Drug Class: Neuroactive steroid (orally active and inhibitory pregnant neurosteroid).

Route of Administration: Oral.

Chemical Formula: C25H35N3O2.

Molar Mass: 409.574 g.mol-1.

Indication:

Zuranolone is typically indicated for the management of postpartum depression in adults.

Associated Conditions:

• Postpartum depression (PPD).

Dose for Postpartum Depression:

• Indicated for treating postpartum depression in adults.

• The recommended dosage of Zuranolone for postpartum depression is 50 milligrams orally once a day in the evening for 14 days.

• It is to be administered with a fat-containing food diet.

• Zuranolone can be used alone or adjunct to other oral antidepressant medications.

• Usage of Zuranolone, further than 14 days in a single course of therapy, has not been determined.

Dosage Modifications:

Renal Impairment:

• No dosage adjustment is required for mild renal impairment cases.

• Reduce the dosage of Zuranolone to 30 milligrams once a day in the evening for moderate to severe cases with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2.

Hepatic Impairment:

• No dosage modification is recommended for mild and moderate cases of hepatic declines.

• Decrease the dosage to 30 mg once a day in the evening for severe hepatic impairment.

Coadministration With CYP3A4 Inducers:

• It is recommended to avoid coadministration of Zuranolone and CYP3A4 inducers.

Coadministration With CYP3A4 Inhibitors:

• Reduce the dosage of Zuranolone to 30 mg qPM when used with potent CYP3A4 inhibitors.

• No dosage adjustment is necessary when Zuranolone is used with moderate CYP3A4 inhibitors.

Dosing Considerations:

• Consider decreasing the dosage of Zuranolone to 40 mg in case of occurrence of central nervous system depressant effects within the total period of 14 days.

• Zuranolone might induce embryo-fetal harm when used in pregnant females. So, advise effective contraceptive methods during the therapy and for a minimum of one week following the final dosage.

What Are the Pharmacological Aspects of Zuranolone?

Pharmacodynamics

Zuranolone is known for not inducing any clinically significant prolongation of QTc interval with two times the maximum recommended dosage. The clinical findings suggest that the coadministration of a recurrent daily dosage of 50 mg of Zuranolone with Alprazolam or alcohol can result in a decline in psychomotor activity.

Mechanism of Action:

The mechanism of action of the drug Zuranolone is not completely determined. However, the mechanism of Zuranolone is known to be associated with its positive allosteric modulation of GABA(A) receptors.

Zuranolone binds to the alpha-beta subunit interface of all the GABA(A) receptors rather than the alpha-gamma subunit interface. Hence, Zuranolone could show affinity for both synaptic GABA(A) receptors that are composed of two alpha, two beta, and gamma subunits and extrasynaptic GABA(A) receptors composed of two alpha, two beta, and delta subunits.

Distribution:

• The volume of distribution of the drug Zuranolone after oral administration is more than 500 liters.

• Hence, the average blood-to-plasma concentration ratio can range between 0.54 and 0.58.

• The plasma protein binding capacity of Zuranolone is a key value greater than 99.5 percent.

Metabolism:

• Zuranolone undergoes well and extensive metabolism, with CYP3A4 as a chief enzyme.

• The findings show that there can be no circulating metabolites more than ten percent of the total drug content, and none shows therapeutic effects on Zuranolone.

Elimination:

• After oral administration of radiolabeled Zuranolone, around 45 percent of the total dosage was recovered in the urine only as metabolites with inappreciable unchanged Zuranolone and 41 percent in feces with markedly less than two percent as unchanged Zuranolone.

Half-Life and Clearance:

• The terminal half-life of the drug Zuranolone is around 19.7 to 24.6 hours in adults.

• The median and apparent clearance of Zuranolone is 33 liters per hour.

Adverse Effects:

Zuranolone is known to precipitate some adverse reactions. The adverse effects observed in greater than ten percent of individuals include:

• Dizziness.

• Somnolence (a state of drowsiness).

The adverse effects of Zuranolone seen in one to ten percent of individuals include:

• Fatigue.

• Diarrhea.

• Abdominal pain.

• Memory declines.

• Muscle twitching.

• Myalgia (muscle aches and pains).

• Rashes.

• Anxiety.

• Tremors.

• Hypoesthesia.

• Urinary tract infection.

What Are the Contraindications of Zuranolone?

No contraindications have been determined so far due to the administration of Zuranolone. However, this drug is not usually recommended for pregnant women due to its embryo-fetal toxicity.

Warnings and Precautions:

CNS Depressant Effects:

• Central nervous system (CNS) depressant effects like confusion and somnolence have been reported.

• So, individuals might have a greater risk of falls.

• CNS depressants like opioids, alcohol, benzodiazepines, and tricyclic antidepressants or drugs increasing the concentration of Zuranolone might significantly impact the psychomotor function and the CNS depressant effects.

The following measures can be taken to reduce or mitigate the CNS depression effects.

• Consider discontinuation of treatment or dosage reduction when CNS depressant effects occur.

• Consider decreasing the dosage when usage with other CNS depressants is inevitable.

• Reduce the dosage in individuals taking potent CYP3A4 inhibitors.

Suicidal Thoughts:

• The incidence of suicidal thoughts and behaviors has been reported with the long-term administration of antidepressant medications like selective serotonin reputable inhibitors (SSRIs), according to the placebo-controlled clinical study.

• But, Zuranolone is not known to show any direct effect on the monoaminergic system. Hence, the risk of suicidal thoughts and behaviors from Zuranolone exposure is still undetermined.

• In individuals with worsening stages of depression and those who encounter incipient suicidal thoughts and behaviors, consider modifying the therapeutic regimen or discontinuing the treatment.

Significant Warnings:

• Zuranolone sometimes causes driving impairment due to its central nervous system depressant effects.

• Hence, advise individuals not to drive or do potentially dangerous things for a minimum of 12 hours after oral administration. This should be considered for the full course of 24 days of therapy.

• Inform the patients about the extent of the driving problem and tell them that they might not be able to meet their driving compliance.

What Are the Drug Interactions of Zuranolone?

Zuranolone is known to interact with certain drugs, resulting in undesirable reactions. The important drug interactions of Zuranolone are listed below.

CNS Depressants:

• Avoid such coadministration or adjust the dosage.

• Coadministration with CNS depressant drugs like alcohol, benzodiazepines, and opioids might precipitate additional pharmacological reactions, causing psychomotor performance impairment.

• Consider decreasing the dosage of Zuranolone in case of an inevitable situation.

CYP3A4 Inducers:

• Avoid coadministration with CYP3A4 inducers.

• This is because CYP3A4 inducers tend to lower the systemic exposure and efficacy of Zuranolone.

Strong CYP3A4 Inhibitors:

• Modify the dosage of Zuranolone when used with string CYP3A4 Inhibitors.

• Potent CYP3A4 inhibitors tend to increase the systemic exposure of Zuranolone, increasing the likelihood of adverse effects.