KYNAMRO (mipomersen sodium) Injection 200 mg/mL may cause serious side effects, including liver problems such as increased liver enzymes or increased fat in the liver.
In the KYNAMRO clinical trial in patients with HoFH, 4 (12%) of the 34 patients treated with KYNAMRO (compared with 0% of the 17 patients treated with placebo) had at least 1 elevation in levels of liver enzymes that was at least 3 times higher than normal. There were no important changes in other measures of liver function.
KYNAMRO also increases liver fat, with or without accompanying increases in liver enzymes. In the trials in patients with heterozygous familial hypercholesterolemia (HeFH) and high cholesterol, the median absolute increase in liver fat was 10% after 26 weeks of treatment, from 0% at baseline, measured by magnetic resonance imaging (MRI). Fatty liver is a risk factor for advanced liver disease.
Your doctor will measure your liver enzyme levels and liver function before starting treatment and then regularly during treatment, as recommended. If enzyme levels or liver function are abnormal, treatment will be withheld or discontinued depending on severity.
Because of the risk of liver problems, KYNAMRO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS.
Do not take KYNAMRO if you:
- Have moderate or severe liver problems or active liver disease, including unexplained abnormal liver tests
- Are allergic to mipomersen or any of the ingredients in KYNAMRO
WARNINGS AND PRECAUTIONS
KYNAMRO can cause increases in liver enzymes and liver fat.
Prior to starting your therapy with KYNAMRO, your doctor should perform liver tests including measurements of liver enzymes called alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase. If the results of any of these tests are abnormal, your doctor may perform additional tests to explain or resolve these abnormalities before starting your treatment with KYNAMRO.
During the first year of therapy, your doctor will conduct liver-related tests on a monthly basis.
After the first year, these tests should be conducted at least once every 3 months. Your doctor should stop your treatment with KYNAMRO if the tests show significant or constant increases in enzyme levels levels.
If liver enzyme levels are elevated and you are showing symptoms of liver injury or liver disease (e.g,, nausea, vomiting, fever, loss of appetite, feeling more tired than usual, yellowing of your eyes or skin, dark urine, itching, or stomach pain), your physician should stop treatment and identify the possible cause.
Drinking alcohol may increase your chance of having liver problems or make your liver problems worse. You should not have more than 1 alcoholic drink each day while using KYNAMRO.
Caution should be exercised when KYNAMRO is used with other medications that may cause liver problems as the effect of these combinations is unknown. More frequent liver-related tests may be necessary.
Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Before starting a new medicine while taking KYNAMRO, even if you will only be taking it for a short time, ask your doctor or pharmacist if it is safe to take while you are using KYNAMRO.
The effect of taking KYNAMRO at the same time as other LDL-lowering drugs that can increase liver fat has not been studied. Therefore, it is not recommended.
Skin reactions at the site of injection were reported at least once in 84% of patients, including redness or discoloration of the skin, pain, tenderness, itching, and swelling around the injection site. Proper injection technique is recommended to help minimize the potential for reactions at the site of injection. These reactions did not occur on all injections. A total of 5% of patients discontinued therapy due to injection site reactions.
Flu-like symptoms, including fever, chills, aches, and tiredness, have been reported in 30% of patients taking KYNAMRO. These symptoms did not occur with all injections. These symptoms usually happen within 2 days after an injection. A total of 3% of patients discontinued therapy due to flu-like symptoms.
USE IN SPECIFIC POPULATIONS
Before you take KYNAMRO tell your doctor if you are pregnant or plan to become pregnant. KYNAMRO may cause harm to your unborn baby. If you are a female who can get pregnant, you should use effective birth control while using KYNAMRO. Talk with your doctor to find the best method of birth control for you. If you become pregnant while taking KYNAMRO, stop taking KYNAMRO and call your doctor right away.
Before you take KYNAMRO tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if KYNAMRO passes into your breast milk. You and your doctor should decide if you will use KYNAMRO or breastfeed. You should not do both.
The safety and effectiveness of KYNAMRO in children under the age of 18 has not been established.
It is not known whether KYNAMRO is safe and effective in people with kidney problems, including people who are receiving kidney dialysis.
In drug trials the most commonly reported side effects were injection site reactions (84%), flu-like symptoms (30%), nausea (14%), headache (12%), and elevations in liver enzymes, specifically ALT (10%).
Tell your doctor right away about any side effect that bothers you or that does not go away.
See full Prescribing Information and Medication Guide, including Boxed Warning, for more details.