Understanding Veozah and its Metabolism
Veozah, with the active ingredient fezolinetant, is a non-hormonal prescription medication used to treat moderate to severe vasomotor symptoms associated with menopause, such as hot flashes and night sweats. It works by blocking the neurokinin 3 (NK3) receptor in the brain, helping to regulate body temperature.
The body metabolizes Veozah primarily through the cytochrome P450 1A2 (CYP1A2) enzyme in the liver. Substances that interfere with this enzyme, particularly inhibitors, can slow down the breakdown of Veozah, leading to higher levels of the drug in the bloodstream. This potential for drug accumulation is the main reason certain medications are contraindicated with Veozah.
The Critical Contraindication: CYP1A2 Inhibitors
The most significant contraindication for Veozah is the use of medications that inhibit the CYP1A2 enzyme. These inhibitors can be classified as weak, moderate, or strong, and all should be avoided when taking Veozah to prevent potentially severe increases in Veozah concentration and the risk of serious side effects.
Examples of Contraindicated CYP1A2 Inhibitors
Numerous medications can inhibit CYP1A2. Some of the notable examples that should not be taken with Veozah include:
- Fluvoxamine (Luvox): A strong CYP1A2 inhibitor used for obsessive-compulsive disorder.
- Mexiletine (Mexitil): An antiarrhythmic drug that inhibits CYP1A2.
- Ciprofloxacin (Cipro): A moderate CYP1A2 inhibiting antibiotic.
- Cimetidine (Tagamet HB): An H2 receptor blocker for stomach issues.
- Combined Hormonal Contraceptives: Birth control containing ethinyl estradiol can inhibit CYP1A2.
- Other Medications: Rucaparib, zileuton, peginterferon alfa-2a, acyclovir, and allopurinol are also listed as CYP1A2 inhibitors that may interact with Veozah.
Contraindicated Health Conditions
Veozah should not be used in individuals with certain pre-existing medical conditions due to increased risk.
Known Cirrhosis
Patients with known cirrhosis should not take Veozah because the drug is metabolized by the liver, and there is a risk of elevated liver enzymes and, in rare postmarketing cases, serious liver injury.
Severe Renal Impairment and End-Stage Renal Disease
Individuals with severe kidney problems (eGFR < 30 mL/min/1.73m²) are also advised against using Veozah as their kidneys cannot effectively clear the drug, leading to higher concentrations and increased risk of side effects.
Important Drug and Supplement Interactions
Beyond strict contraindications, other substances require caution and discussion with a healthcare provider:
- Acetaminophen (Tylenol): Combining with Veozah may increase the risk of liver damage.
- Combined Hormonal Contraceptives: Can increase Veozah side effects due to CYP1A2 inhibition.
- Piperine (Black Pepper Extract): Can inhibit CYP1A2.
- Caffeine: A weak CYP1A2 inhibitor that can also trigger hot flashes.
- Alcohol and Cannabis (CBD): Both are liver-metabolized, and potential interactions or increased risk of liver issues should be discussed with a doctor.
Comparison of Key CYP1A2 Inhibitors and Safer Alternatives
It's important to be aware of which medications are contraindicated and to discuss potential alternatives with a doctor. The table below provides examples:
| Medication Class | Contraindicated Examples (CYP1A2 Inhibitors) | Safer Alternatives (Consult Your Doctor) |
|---|---|---|
| Antibiotics | Ciprofloxacin, Norfloxacin, Enoxacin | Other antibiotic classes, such as penicillin-based or cephalosporin agents |
| Antidepressants | Fluvoxamine | Selective serotonin reuptake inhibitors (SSRIs) like paroxetine (Brisdelle) are alternative non-hormonal treatments for hot flashes, but interactions vary |
| H2 Blockers | Cimetidine (Tagamet HB) | Famotidine (Pepcid) |
| Antiarrhythmics | Mexiletine, Amiodarone | Other antiarrhythmic agents, but always discuss with your cardiologist |
| Hormonal Contraceptives | Combined hormonal contraceptives (containing ethinyl estradiol) | Progestin-only contraceptives (discuss with your gynecologist) |
Importance of Medical Monitoring and Patient Awareness
Given the potential for liver injury, baseline liver function tests are necessary before starting Veozah. Monthly testing is recommended for the first three months, followed by tests at six and nine months. Patients should be vigilant for symptoms of liver problems, including fatigue, jaundice, nausea, vomiting, itching, pale stools, dark urine, or abdominal pain. If these symptoms appear, Veozah should be stopped, and a doctor consulted immediately. Maintaining an accurate list of all medications and supplements is vital, as is open communication with healthcare providers.
Conclusion
Knowing what meds are contraindicated with Veozah is crucial for safe treatment of menopausal vasomotor symptoms. Medications and substances that inhibit the CYP1A2 enzyme are the primary concern, as they can lead to dangerous levels of Veozah in the body. Conditions like liver cirrhosis and severe renal impairment also contraindicate Veozah use. By understanding these risks, undergoing regular monitoring, and communicating openly with healthcare providers, patients can manage their menopausal symptoms safely.
