Hereditary angioedema is a rare genetic disorder which causes rogue collections of fluid outside of the blood vessels. These deposits can become so large that they actually begin to block the blood vessels, which can lead to serious complications. This condition is the result of lower than average levels of the complex protein known as the C1 Esterase Inhibitor. As a result, patients with this condition are treated with injections of the C1 Esterase Inhibitor.
C1 Esterase Inhibitor is injected intravenously into the bloodstream. It is a naturally occurring protein and is typically derived from donated human plasma, which carries some risks but means the patient is at less risk of side effects.
C1 Esterase Inhibitor is available under the brand names Berinert (CSL Behring) and Cinryze (ViroPharma), among others.
Injections of the C1 Esterase Inhibitor can cause a wide range of different side effects. Patients who experience any of the following side effects should contact their doctor immediately. The following side effects often require medical attention:
Injections of the C1 Esterase Inhibitor can put a heavy load on the body. It can take time for the body to adapt to the injections, and the body may adapt in a way that causes unwanted side effects. Patients who experience the following side effects should consult with their doctor to determine the best way to mitigate or avoid the following side effects:
This is not necessarily a complete list of side effects. If patients begin to experience new symptoms after receiving C1 Esterase Inhibitor injections, they should report those symptoms to the doctor immediately. Patients can report new side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
For preventative use against HAE, 1,000 units (10 ml) of the Cinryze (the branded form of C1 Esterase Inhibitor) are usually injected intravenously at a rate of 1 ml per minute.
Cinryze is usually good for three hours after it has been reconstituted. The solution should be injected before that time. Any solution which has not been injected should be discarded.
For treatment of acute attacks of hereditary angioedema, Berinert (another branded form of C1 Esterase Inhibitor) is typically used. The dose is typically determined by a doctor, but standard practice suggests 20 IUs of berinert per kilogram of the patient’s body weight. The injection is typically given at a rate of 4 ml (500 IUs equals 10 ml) per minute, intravenously.
Injections of C1 Esterase Inhibitor have not been fully evaluated in children, however, the standard 20 IUs per kg in body weight is thought to hold true in children.
Berinert is usually good for eight hours after it has been reconstituted. The solution should be injected before that time. Any solution which has not been used within eight hours should be discarded.
Long-term prophylaxis requires the patient to be able to do home treatment. Patients should not begin home treatment until they fully understand how the injections of C1 Esterase Inhibitor work and the myriad of risks that come with it. Patients should be comfortable and practice performing the injection on themselves before they begin to administer the prophylactic treatments themselves.
Patients who accidentally miss a dose of C1 Esterase Inhibitor should consult their doctor to determine how best to proceed.
Patients should follow the directions of their doctor in terms of dosages. The numbers given here are representative of the typical dose and dosing structure for C1 Esterase Inhibitor.
C1 Esterase Inhibitor can interact with a wide range of different drugs in a variety of different ways. The biggest risk of interaction between C1 Esterase Inhibitor injections and other drugs is the increased risk of blood clots, followed by medications which will outright neutralize the injection. Not all interactions are necessarily known, though. Patients should be sure to disclose all drugs, medications, and supplements they are currently taking to their doctor, along with any and all medical conditions they suffer from before receiving C1 Esterase Inhibitor injections.
Patients who are taking carfilzomib (a cancer drug) should exercise extreme caution when deciding whether or not to receive injections of C1 Esterase Inhibitor. By taking the two drugs concurrently, patients seriously heighten their risk of developing dangerous blood clots (a side effect of carfilzomib). This risk is compounded in patients who smoke or who have high blood pressure or cholesterol. If a patient were to develop a blood clot it could lead to serious complications such as heart attacks or strokes. Patients should disclose a full list of the medications, drugs, and supplements they are taking before they decide to receive C1 Esterase Inhibitor injections. Patients should also make sure their doctor is fully apprised of all medical conditions and health concerns they are facing.
The drugs lenalidomide, pomalidomide, and thalidomide all interact with C1 Esterase Inhibitor injections like carfilzomib does.
The following drugs also put the user at increased risk of blood clot if used concurrently with C1 Esterase Inhibitor injections, albeit at a lower risk relative to the medications listed above: bazedoxifene, chlorotrianisene, danazol (a drug used to treat endometriosis), darbepoetin alfa, epoetin alfa and other forms of epoetin, dehydroepiandrosterone, diethylstilbestrol, esterified estrogens, estradiol (along with other forms of estradiol), estrone, estropipate, fluoxymesterone, methyltestosterone, mestranol, nandrolone, ospemifene, oxandrolone, oxymetholone, peginesatide, quinestrol, raloxifene, stanozolol, tamoxifen, testosterone, testolactone, toremifene.
Patients who begin to experience symptoms of a blood clot, such as chest pain, difficulty breathing, coughing up blood, or sudden numbness/weakness on one side of the body should contact their doctor immediately.
Patients who are taking alteplase (a drug which dissolves blood clots) should be aware that the two medicines combine in the blood, completely negating the effects of both medications. Patients should avoid taking alteplase concurrently with C1 Esterase Inhibitor injections. Patients should consult with their doctor to determine the best alternatives if the medications both need to be taken over the same period.
Anistreplase, reteplase, streptokinase, tenecteplase, and urokinase all interact with C1 Esterase Inhibitor injections like alteplase does: by binding to the injected material and neutralizing both medications.
This is not necessarily a complete list of interactions. Patients should make sure their doctor is fully apprised of all medications, drugs, and supplements they are taking before they begin to receive injections of the C1 Esterase Inhibitor. Patients should consult with their doctor if they have any questions or concerns about any medication they are taking.
C1 Esterase Inhibitor is derived from human plasma. Although plasma donors are thoroughly screened, and the donated plasma is rigorously tested and treated, it is possible that diseases may remain in the plasma from their original donor. These diseases can be transmitted to the C1 Esterase Inhibitor injection materials and go on to infect the patients. Patients should be vigilant for signs of new infections or diseases, and contact their doctor immediately if they think they may have been infected. In particular, the agent which causes Creutzfeld-Jacob disease (also known as mad cow disease) is thought to be able to be transmitted in this manner).
Serious thrombotic events (formation of a rogue blood clot) have occurred in patients who are receiving C1 Esterase Inhibitor injections. Patients with a history of thrombosis, or who already have risk factors such as obesity or are taking oral contraceptives should be closely monitored in their use of C1 Esterase Inhibitor. Patients who are at risk of thrombotic events may want to consider alternative treatment or consult with their doctor to determine how to minimize risk.
Patients who are performing the injections themselves as part of an at home therapy plan should be extremely careful to only use the dose prescribed by their doctor. Patients who use larger doses put themselves at risk of greater side effects. Increased dosage has also been tied to increased risks of serious thrombotic events. If patients are unsure of how much of the medication they need to use they should consult with their doctor before injecting.
Injections of the C1 Esterase Inhibitor have been known to cause serious allergic reactions. Patients should be vigilant for signs of an allergic reaction, which can include outbreaks of hives, rashes, and swelling of the the neck, throat, or face. Patients who begin to experience these symptoms should contact their doctor or other trained medical professionals immediately. Patients who receive C1 esterase inhibitor injections are advised to carry epinephrine (epipen) with them at all times.
Patients should ensure they are using a fresh, new needle for every injection. By using needles which may be dirty patients put themselves at serious risk of infection. By using old needles, or even sharing needles, patients put themselves at risk of contracting serious blood borne illnesses.
Attacks of hereditary angioedema are serious and injections of the C1 Esterase Inhibitor are not a guarantee against such attacks. Patients who experience symptoms of a hereditary angioedema attack should contact their doctor immediately to receive treatment for the attack.
Injections of the C1 Esterase Inhibitor are considered a category c drug in terms of pregnancy. This means that there insufficient evidence to determine whether or not is safe for human fetuses when taken during pregnancy by the mother. Patients who are pregnant, intend to become pregnant, or may become pregnant should consult with their doctor before beginning injections of the C1 Esterase Inhibitor. Additionally, patients who are breastfeeding should consult with their doctor before receiving injections of the C1 Esterase Inhibitor. It is not known whether or not the medication can be transmitted through breast milk or whether or not it will have any effect on the baby consuming it.
Vials of the C1 Esterase Inhibitor should be stored between 36 and 77 degrees Fahrenheit.
Haegarda, a specific brand of C1 Esterase Inhibitor simply needs to be stored below 86 degrees Fahrenheit and away from sunlight.
Neither the vials of reconstituted solution should ever be frozen.
Patients Hereditary Angioedema have are all but forced into receiving injections of the C1 Esterase Inhibitor. The condition is serious, and other treatments less effective or non-existent. With that said, the drug is not altogether punishing. The most common side effect (with less than 5% of patients reporting it) is a changed or diminished sense of taste. Other side effects tend to be similarly mild.
Like any drug, especially one delivered via intravenous injection, it demands respect. Patients must be able to deliver the injection carefully and consistently. They must take great pains with respect to cleanliness and dose. If the patient is able to do this, however, their risk of serious infection is relatively low.
C1 Esterase inhibitor is derived from human plasma, though. There is a risk of diseases (including mad cow disease) being transmitted via injection, something that is largely outside of the patient’s control. There are no known cases of this occurring, though, and given the rigorous standards and treatments for plasma, the risk is quite small. In all, much of the risk of adverse effects is in the hands of whoever is performing the inject: be it a medical professional or the patient themselves.