Usage
This combination is primarily used in the treatment of female infertility, specifically in patients with polycystic ovary syndrome (PCOS) who are resistant to clomiphene citrate alone. Acetylcysteine is used as an adjuvant to clomiphene to improve ovulation rates. Acetylcysteine itself is a mucolytic agent and antioxidant, while enclomiphene is a selective estrogen receptor modulator (SERM).
Alternate Names
- Acetylcysteine: N-acetyl cysteine, N-acetylcysteine, NAC
- Enclomiphene: Androxal (brand name), Zuclomiphene citrate
- Combination: No established alternate name for the combination.
How It Works
Acetylcysteine:
- Pharmacodynamics: Acts as a mucolytic by breaking disulfide bonds in mucus, making it less viscous. Also exhibits antioxidant properties by replenishing glutathione stores.
- Pharmacokinetics: Well-absorbed orally. Metabolized in the liver and excreted primarily in the urine.
Enclomiphene:
- Pharmacodynamics: The more active isomer of clomiphene, enclomiphene primarily acts as an estrogen receptor antagonist in the hypothalamus. This reduces negative feedback inhibition, leading to increased gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) release. Increased FSH and LH stimulate follicular development and ovulation.
- Pharmacokinetics: Administered orally. Metabolized in the liver and excreted primarily through the biliary route. The zuclomiphene isomer has a longer half-life than enclomiphene.
Combination: While both drugs are used concurrently, their mechanisms of action are independent. Acetylcysteine’s role is hypothesized to improve insulin sensitivity and reduce oxidative stress in PCOS patients, thereby enhancing the efficacy of enclomiphene in inducing ovulation.
Dosage
Standard Dosage
Adults:
- Enclomiphene: 12.5 mg to 25 mg orally per day, typically starting on day 3 of the menstrual cycle for 5 days.
- Acetylcysteine: 1200 mg/day orally for 5 days concurrently with enclomiphene, starting on day 3 of the menstrual cycle.
Children: This combination is not indicated for use in children.
Special Cases:
- Elderly Patients: Not typically used in this population for infertility.
- Patients with Renal Impairment: Caution is advised; dose adjustment of acetylcysteine may be necessary.
- Patients with Hepatic Dysfunction: Caution is advised as both drugs are metabolized in the liver.
- Patients with Comorbid Conditions: Individualized dosing based on specific conditions.
Clinical Use Cases
The combination of acetylcysteine and enclomiphene is specifically used for ovulation induction in infertile women with PCOS. It is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments may be necessary based on patient response, tolerance, and comorbidities, especially liver and kidney dysfunction.
Side Effects
Common Side Effects
- Acetylcysteine: Nausea, vomiting, stomach upset, hypersensitivity reactions.
- Enclomiphene: Hot flashes, bloating, stomach ache, blurred vision.
Rare but Serious Side Effects
- Enclomiphene: Ovarian hyperstimulation syndrome (OHSS), visual disturbances.
Long-Term Effects
No long-term effects have been specifically reported for this combination.
Adverse Drug Reactions (ADR)
Any severe adverse reactions, such as OHSS or allergic reactions, require immediate medical attention.
Contraindications
- Acetylcysteine: Hypersensitivity to acetylcysteine.
- Enclomiphene: Pregnancy, liver disease, abnormal uterine bleeding, ovarian cysts (excluding those in PCOS), hormone-sensitive tumors, uncontrolled thyroid or adrenal dysfunction.
Drug Interactions
- Acetylcysteine: May interact with nitroglycerin.
- Enclomiphene: May interact with other hormonal medications.
Pregnancy and Breastfeeding
Enclomiphene is contraindicated during pregnancy and breastfeeding. Acetylcysteine should be used with caution during pregnancy and breastfeeding, and only if the potential benefit outweighs the risk.
Drug Profile Summary
- Mechanism of Action: Acetylcysteine - Mucolytic and antioxidant; Enclomiphene - SERM, increases FSH and LH.
- Side Effects: Hot flashes, bloating, nausea, vomiting, stomach ache, blurred vision, hypersensitivity.
- Contraindications: Pregnancy, liver disease, abnormal uterine bleeding, ovarian cysts, hormone-sensitive tumors, uncontrolled thyroid or adrenal dysfunction, hypersensitivity to acetylcysteine.
- Drug Interactions: Limited information available on interactions for the combination.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Enclomiphene: 12.5-25 mg/day; Acetylcysteine: 1200mg/day, both for 5 days starting on day 3 of the cycle.
- Monitoring Parameters: Follicle growth, estrogen levels, endometrial thickness, pregnancy test.
Popular Combinations
This particular combination is not commonly cited as a “popular” one in the general sense. Rather, it is specifically investigated and utilized in particular clinical scenarios of clomiphene-resistant PCOS. Clomiphene + metformin is another combination used in PCOS.
Precautions
Monitor for ovarian hyperstimulation syndrome. Evaluate liver and kidney function before starting treatment. Advise patients about potential side effects.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Acetylcysteine + Enclomiphene for ovulation induction?
A: Enclomiphene 12.5-25 mg/day and Acetylcysteine 1200 mg/day, both given orally for 5 days starting on day 3 of the menstrual cycle.
Q2: How does this combination improve ovulation rates in PCOS patients?
A: Enclomiphene stimulates ovulation by increasing FSH and LH secretion. Acetylcysteine’s role is hypothesized to improve insulin sensitivity and reduce oxidative stress, which may enhance enclomiphene’s efficacy.
Q3: What are the common side effects patients should be aware of?
A: Hot flashes, abdominal bloating, nausea, vomiting, stomach discomfort, and changes in vision.
Q4: Are there any contraindications for this drug combination?
A: Yes. Pregnancy, liver disease, abnormal uterine bleeding, ovarian cysts (excluding those in PCOS), hormone-sensitive tumors, uncontrolled thyroid or adrenal dysfunction, and hypersensitivity to acetylcysteine are contraindications.
Q5: What monitoring is necessary during treatment?
A: Follicle growth monitoring via ultrasound, serum estrogen levels, endometrial thickness measurement, and pregnancy testing are recommended.
Q6: Can this combination be used in patients with renal or hepatic impairment?
A: Caution is advised. Dosage adjustments may be necessary, especially for acetylcysteine in renal impairment. Close monitoring of liver function is essential in patients with hepatic dysfunction.
Q7: How does enclomiphene differ from clomiphene citrate?
A: Enclomiphene is the more active isomer of clomiphene citrate and is believed to have fewer side effects.
Q8: What is the role of acetylcysteine in this combination?
A: While its exact role is not fully understood, it is hypothesized that acetylcysteine improves insulin sensitivity and reduces oxidative stress, potentially improving ovulation rates in PCOS patients.
Q9: How long should this combination be used for?
A: Treatment typically follows the standard clomiphene citrate protocol of 5 days starting on day 3 of the menstrual cycle. Several cycles may be attempted depending on the patient’s response.
