Cortisol is your body’s stress hormone. Your adrenal glands make it, and it affects many of your body functions. Cortisol lowers inflammation and increases your blood sugar and blood pressure. It is normal for your cortisol levels to change throughout the day.
Cushing’s syndrome is a hormonal problem where you have high levels of cortisol in your blood (hypercortisolemia) for too long. Recorlev (levoketoconazole) is a medicine used to lower cortisol levels in your blood if you have Cushing’s syndrome and surgery has not helped or is not an option for you. Read to learn more about using Recorlev to lower cortisol levels with Cushing’s syndrome.
How Does Recorlev Work to Lower Cortisol Levels?
Your pituitary, a small gland at the base of your brain, makes adrenocorticotropic hormone (ACTH). This hormone tells your adrenal glands (which sit at the top of your kidneys) to make cortisol. Recorlev is a cortisol synthesis inhibitor, which means it lowers the amount of cortisol that your body makes. It does this by blocking key steps involved in making cortisol. These key steps involve different enzymes, including 11β-hydroxylase (CYP11B1), 17α-hydroxylase (CYP17A1), and the cholesterol side‑chain cleavage enzyme (CYP11A1). By blocking these enzymes, Recorlev helps lower the amount of cortisol in your blood.
How Was Recorlev Studied to Lower Cortisol Levels?
Two studies, LOGICS and SONICS, evaluated Recorlev to lower cortisol levels in people with Cushing’s syndrome. People with pituitary or adrenal cancer were not allowed in the studies. All people had an average 24-hour urinary free cortisol (UFC) level of at least 1.5 times the upper limit of normal. The normal range is 11 to 138 nmol/24 hours. The table below reviews important characteristics of the people enrolled in these studies.
Cause of Cushing’s syndrome | LOGICS
Pituitary gland: 83 % Adrenal gland: 10 % ACTH tumor: 2 % Unknown: 5 % | SONICS
Pituitary gland: 85 % Adrenal gland: 9 % ACTH tumor: 1 % Unknown: 5 % |
| Initial number of study participants | 79 | 94 |
| Average age (in years) of study participants | 45 | 44 |
| Race | White: 93 % Black: 5 % Asian: 1 % Unknown: 1% | White: 96 % Black: 1 % Other: 1 % Unknown: 2 % |
| Percentage of female study participants | 76 % | 82 % |
| Average time since Cushing’s syndrome diagnosis | 63 months (5.25 years) | 68 months (5.7 years) |
| 24-hour UFC level at study entry | Average of 747 nmol/24 hours
Half higher and half lower than 441 nmol/24 hours | Average of 671 nmol/24 hours
Half higher and half lower than 408 nmol/24 hours |
SONICS
This study looked at how well Recorlev worked to lower cortisol levels. There were two main phases of the study: a dose titration phase and a maintenance phase. Everyone in the study took Recorlev during the titration phase, starting at a low dose. The Recorlev doses were increased as needed every two to three weeks based on labs to a maximum dose or maximally tolerated dose. People moved on to the maintenance phase for six months. The primary goal of the study was to see how many participants were Recorlev responders, defined as the proportion of people with normalized UFC at the end of the maintenance phase. Normalized UFC was defined as maintaining a normal UFC during the maintenance phase without requiring a dose increase.
LOGICS
In the SONICS study, Recorlev was shown to effectively lower UFC levels in some people. In the LOGICS study, investigators looked at people with controlled UFC levels using Recorlev to see what happened to these levels when treatment was either continued or stopped. A group of 44 people taking stable doses of Recorlev was divided in half: 22 people continued taking Recorlev, and the remaining 22 started taking a placebo (no medicine) instead of Recorlev. The goal of the study was to compare loss of response between those who continued Recorlev and those who switched to placebo. Loss of response was defined as an average UFC of >1.5 times the upper limit of normal.
What Were the Recorlev Study Results?
SONICS
Of the original 94 people, 77 moved from the titration phase to the maintenance phase, and 61 people completed the maintenance phase. The percentages of the original 94 people who had normal UFC at the end of the titration and maintenance phases are below.
Normal UFC | Titration 67 % (63/94) | Maintenance 31 % (29/94) |
To summarize, Recorlev helps achieve normal UFC levels and keep them normalized in some people with Cushing’s syndrome.
LOGICS
Of the 22 people who switched to a placebo, all but one person lost UFC response (95.5%). In contrast, nine of the 22 people who kept taking Recorlev (40.9%) lost UFC response. This shows that most people who respond to Recorlev continue to respond. However, keeping an eye on UFC is important.
Your results may differ from those seen in these studies.
What Should I Know About Side Effects of Recorlev?
Two of the most common side effects of Recorlev are nausea and vomiting. If you have these side effects while taking Recorlev, talk to your health care provider. Follow any instructions about changing your diet and drinking plenty of liquids to stay hydrated. You can take this medicine with or without food, so if taking it with food reduces your nausea, that will not affect how the medicine works to lower your cortisol levels.
Because Recorlev lowers your cortisol levels, these levels can get too low. Symptoms of low cortisol levels can include low blood pressure and low blood sugar. Follow any instructions from your health care provider about checking these.
Your risk of having low cortisol levels or adrenal insufficiency with Recorlev may be higher if you are having a lot of stress, such as an infection or significant mental stress. If you have higher-than-normal levels of stress, tell your health care provider right away. They may want to check your levels more frequently until things get back to normal. Make sure that you keep all appointments to have your blood checked. Carefully follow all directions to have your pee (urine) collected and tested.
There may be other side effects of Recorlev that are not listed here. Contact your health care provider if you think you are having side effects.
Is Recorlev the Right Medicine for Me?
Recorlev is not right for everyone. If you have certain health conditions, take certain medicines, or have a history of certain problems after taking some medicines, it may not be safe for you to take Recorlev.
Recorlev has the potential to cause liver damage. Liver damage from Recorlev may not be related to the dose you take or how long you take it. Keep all appointments to have your labs checked while you are taking it. Your health care provider may need to stop or adjust your dose of Recorlev based on these lab tests. You should not take Recorlev if you have cirrhosis, other liver problems, frequent gallstones, or a history of liver problems after taking ketoconazole (Nizoral) or other similar medicines such as fluconazole (Diflucan), itraconazole (Sporanox, Tolsura), posaconazole (Noxafil), or voriconazole (Vfend), which is a medicine used for fungal infections.
Recorlev seems to be associated with a dangerous heart rhythm, called QT prolongation. This dangerous heart rhythm seems to be more common with higher doses of Recorlev. If you take certain other medicines or have low electrolytes (such as potassium or magnesium), you may also have a higher risk of this dangerous heart rhythm. If you have a history of certain heart rhythm problems, take other medicines that can also prolong your QT interval, or have a first-degree relative with long QT syndrome, you should not take Recorlev. If there is a concern about your heart, your health care provider may do tests to see if Recorlev is safe for you to take.
This is not a complete list of health conditions or medicines that should be considered before you start taking Recorlev. Tell your health care provider about all of your health conditions and any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. This will help them know if Recorlev is right for you.
What Other Considerations Should I Know About?
Before you start and while you are taking Recorlev, you will likely need to collect pee (urine) samples for testing. These pee tests measure cortisol levels to see if the medicine is working for you or if dosing changes are needed. The drugmaker offers Xeris Care Connection to help with your care. This service includes free pickup and delivery of your 24-hour pee collections.
There is also a copay savings program available from the drugmaker that may cost you as little as $0 for your monthly copay for your Recorlev prescription. Whether you are eligible depends on your insurance coverage.
You will not pick up Recorlev from your neighborhood pharmacy. Instead, the drugmaker works with a specialty pharmacy, PantherRx. PantherRx will work with your health care provider and insurance company to make sure they have all of the necessary information to fill your prescription. They will deliver Recorlev directly to your home.
To learn more about these considerations, you can visit the drugmaker’s website at https://www.recorlev.com/one-on-one-support/meet-your-support-team/ or contact them by phone at 844-444-RCLV (844-444-1258).