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Teicoplanin is not for intraventricular use. The manufacturer strongly discourage injecting Teicoplanin into the brain.

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Cerdelga (Eliglustat) - Uses, Dose, Side effects, MOA, Brands

Eliglustat is a medication used in the treatment of Gaucher disease, a rare genetic disorder characterized by the deficiency of an enzyme called glucocerebrosidase. This deficiency leads to the accumulation of certain fatty substances in the body, particularly in the spleen, liver, and bone marrow.

Eliglustat works by inhibiting an enzyme called glucosylceramide synthase, which plays a role in the production of the fatty substances that accumulate in Gaucher disease. By inhibiting this enzyme, eliglustat helps reduce the buildup of these substances and improves symptoms associated with the disease.

Cerdelga (Eliglustat) is an oral medicine that is indicated for the treatment of patients with Gaucher disease type 1 (who are extensive metabolizers).

Cerdelga (Eliglustat) Uses:

Gaucher disease:
- Treatment of adult patients with Gaucher disease type 1 (GD1) the ones who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs).
- Limitations of use:
  - Patients who are CYP2D6 ultra-rapid metabolizers (URMs) may not attain adequate concentrations of eliglustat to achieve a therapeutic effect.
  - A specific dosage cannot be suggested for those patients whose CYP2D6 genotype cannot be determined (indeterminate metabolizers).

Eliglustat Adult dose:

Cerdelga (Eliglustat) Dose in the treatment of Gaucher disease: Oral:

Eliglustat is a medicine used to treat Gaucher disease. It's taken by mouth.

The dosage depends on how your body metabolizes drugs, which can be determined by a test approved by the FDA. There are three types: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs).

For extensive and intermediate metabolizers:

Take 84 milligrams twice a day.
If you miss a dose, take it when you remember, but don't take two doses at once.

For poor metabolizers:

Take 84 milligrams once a day.

If you're taking other medicines that affect the same enzymes in the body, your doctor may adjust your dosage:

If you're an extensive metabolizer and you're taking a strong or moderate inhibitor of CYP2D6 or CYP3A4, take 84 milligrams once a day.
If you're an intermediate metabolizer and you're taking a strong CYP3A inhibitor, don't take eliglustat.
If you're a poor metabolizer and you're taking a strong CYP3A inhibitor, don't take eliglustat. If you're taking a moderate or weak CYP3A inhibitor, it's best to avoid eliglustat.

If you're switching from another enzyme replacement therapy (ERT) like imiglucerase, velaglucerase alfa, or taliglucerase alfa, you can start taking eliglustat 24 hours after your last dose of the previous therapy.

Use in Children:

Not indicated.

Pregnancy Risk Category: B3

In some studies with animals, there were problems noticed during pregnancy.
If someone with uncontrolled type 1 Gaucher disease becomes pregnant, there's a higher chance of the pregnancy not continuing normally.
The mother might have a swollen liver and spleen and low platelet count, which could also affect the pregnancy negatively.

Eliglustat can be used during lactation

We're not sure if eliglustat passes into breast milk.
The manufacturer suggests that if you're breastfeeding and considering taking this medication, you should think about the potential risk to your baby, the advantages of breastfeeding for your baby, and how much the treatment helps you.
Talk to your doctor about what's best for you and your baby.

Cerdelga (Eliglustat) Dose in Kidney disease:

For people with kidney problems, the decision to use eliglustat depends on how their body metabolizes drugs, which can be determined by a test. Here's what to consider:

If you have mild to severe kidney problems (with a creatinine clearance of at least 15 mL/minute):
- Extensive metabolizers: You likely won't need to change your dosage.
- Intermediate metabolizers and poor metabolizers: It's best to avoid using this medication.
If you have end-stage renal disease (with a creatinine clearance less than 15 mL/minute, with or without dialysis):
- Regardless of your metabolizer status, it's recommended to avoid using eliglustat.

Cerdelga (Eliglustat) Dose in Liver disease:

For individuals with liver issues, eligibility for eliglustat usage depends on their body's ability to metabolize drugs (CYP2D6 metabolizer status) and whether they're taking medications that affect certain enzymes. Here's a breakdown:

If you have mild liver impairment (Child-Pugh class A):
- Extensive metabolizers (EMs) without using CYP2D6 or CYP3A inhibitors: No need to adjust dosage.
- EMs using a weak CYP2D6 inhibitor or a strong, moderate, or weak CYP3A4 inhibitor: Take 84 mg once daily.
- EMs using a strong or moderate CYP2D6 inhibitor: Avoid using this medication.
- Intermediate metabolizers (IMs) and poor metabolizers (PMs): Avoid using this medication.
If you have moderate to severe liver impairment (Child-Pugh class B and C):
- Regardless of your metabolizer status, it's not recommended to use eliglustat.

Common Side Effects of Cerdelga (Eliglustat):

Central nervous system:
- Headache
- Fatigue
Gastrointestinal:
- Diarrhea
- Nausea
Neuromuscular & skeletal:
- Arthralgia
- Back pain
- Limb pain

Less Common Side Effects of Cerdelga (Eliglustat):

Cardiovascular:
- Palpitations
Central nervous system:
- Migraine
- Dizziness
Dermatologic:
- Skin rash
Gastrointestinal:
- Flatulence
- Upper abdominal pain
- Dyspepsia
- Gastroesophageal reflux disease
- Constipation
Neuromuscular & skeletal:
- Weakness
Respiratory:
- Oropharyngeal pain
- Cough

Contraindications to Cerdelga (Eliglustat):

In extensive metabolizers (EMs) with moderate or severe liver problems, as well as in intermediate metabolizers (IMs) or poor metabolizers (PMs) with any level of liver issue, it's advised not to use eliglustat.
Also, avoid combining a moderate or strong CYP2D6 inhibitor with a moderate or strong CYP3A inhibitor in EMs or IMs.
If you're an IM or PM, or if you're an EM with mild liver impairment, don't take eliglustat if you're using a strong CYP3A inhibitor.
Additionally, for Canadian users, there are added contraindications: If you're allergic to eliglustat or any ingredient in it, or if you have certain inherited conditions like galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency, don't use this medication.
Also, avoid combining a strong CYP3A4 inhibitor with eliglustat if you're an EM with mild liver impairment.

Warnings and precautions

Arrhythmias:

Eliglustat can lead to changes in certain intervals measured on an electrocardiogram (ECG), such as PR, QTc, and QRS, particularly when there are very high levels of eliglustat in the blood.
These changes can affect the heart's rhythm and may lead to arrhythmias.

Cardiovascular disease

If you have preexisting heart conditions like congestive heart failure (CHF), recent acute myocardial infarction (MI), bradycardia (slow heart rate), heart block, or ventricular arrhythmia, or if you have long QT syndrome, it's recommended to avoid using eliglustat.
Additionally, it's advised not to combine eliglustat with certain medications used to treat irregular heart rhythms, such as Class IA antiarrhythmics like quinidine and procainamide, and Class III antiarrhythmics like amiodarone and sotalol, as the safety of this combination hasn't been studied.

Hepatic impairment

If you're an extensive metabolizer (EM) with moderate to severe liver impairment, or if you're an intermediate metabolizer (IM) or poor metabolizer (PM) with any level of liver impairment, the use of eliglustat is not recommended.
Additionally, if you're an EM with mild liver impairment and you're taking a moderate or strong CYP2D6 inhibitor, it's also not advised to use eliglustat.

Renal impairment

If you're an intermediate metabolizer (IM) or poor metabolizer (PM) with any level of kidney impairment, or if you're an extensive metabolizer (EM) with end-stage renal disease (ESRD), it's recommended to avoid using eliglustat.

Eliglustat: Drug Interaction

Note: Drug Interaction Categories:

Risk Factor C: Monitor When Using Combination
Risk Factor D: Consider Treatment Modification
Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Ajmaline	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
ARIPiprazole	CYP2D6 inhibitors (Weak), may increase serum levels of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph.
Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Brentuximab Vedotin	Brentuximab Vedotin may be increased by P-glycoprotein/ABCB1 inhibitors. Concentrations of the monomethyl auristatin E component (MMAE) may increase.
Celiprolol	The serum concentration of Celiprolol may be increased by P-glycoprotein/ABCB1 inhibitors
CloBAZam	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Clofazimine	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Moderate CYP3A4 Inducers	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Everolimus	Everolimus serum concentration may be increased by P-glycoprotein/ABCB1 inhibitors
Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Haloperidol	QT-prolonging agents (Indeterminate risk - Avoid) can increase the QTcprolonging effects of Haloperidol.
Ivosidenib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Larotrectinib	The serum concentration of Larotrectinib may be increased by P-glycoprotein/ABCB1 inhibitors
Lumefantrine	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Naldemedine	The serum concentrations of Naldemedine may be increased by P-glycoprotein/ABCB1 inhibitors.
Naloxegol	The serum concentrations of Naloxegol may be increased by P-glycoprotein/ABCB1 inhibitors.
Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Panobinostat	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Peginterferon Alfa-2b	High risk with inhibitors. May lower serum concentrations of CYP2D6 substrates. Peginterferon Alf-2b could increase serum concentrations of CYP2D6 Substrates.
P-glycoprotein/ABCB1 Substrates	P-glycoprotein/ABCB1 inhibitors may increase serum levels of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors can also increase the distribution of p.glycoprotein substrates in specific cells/tissues/organs that have high levels (e.g. brain, T-lymphocytes and testes). Loperamide is an exception.
Prucalopride	The serum concentrations of Prucalopride may be increased by P-glycoprotein/ABCB1 inhibitors.
Agents that prolong QT (Highest risk)	QT-prolonging agents (Indeterminate risk - Avoid) can increase the QTc prolonging effect QT-prolonging agents (Highest risk). When using these agents together, be sure to monitor for QTc interval prolongation or ventricular arrhythmias. Patients at higher risk for QTc prolongation might have additional risk factors.
QuiNINE	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Ranolazine	Ranolazine may be increased by P-glycoprotein/ABCB1 inhibitors.
RifAXIMin	The serum concentrations of RifAXIMin may be increased by P-glycoprotein/ABCB1 inhibitors
Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Silodosin	The serum concentrations of Silodosin may be increased by P-glycoprotein/ABCB1 inhibitors.
Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Simeprevir	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Talazoparib	Talazoparib serum concentration may be increased by P-glycoprotein/ABCB1 inhibitors. Management: The following exceptions are addressed in separate interaction monographs.
Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Risk Factor D (Consider therapy modifications)
Abiraterone Acetate	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. When possible, avoid concurrent use of abiraterone and CYP2D6 Substrates with a narrow therapeutic index. If concurrent use cannot be avoided, closely monitor patients for signs and symptoms of toxic effects.
Afatinib	The serum concentrations of Afatinib may be increased by P-glycoprotein/ABCB1 inhibitors. If afatinib is not tolerated, reduce the dose by 10mg according to US labeling. Canadian labeling states that it is best to avoid combination therapy. If you must use the P-gp inhibitor, do so simultaneously with or after afatinib.
Asunaprevir	High risk of Inhibitors increasing serum concentrations of CYP2D6 Substrates
Betrixaban	The serum concentration of Betrixaban may be increased by P-glycoprotein/ABCB1 inhibitors. Management: Reduce the initial dose of betrixaban to 80 mg, followed by 40 mg daily if taken with a Pglycoprotein inhibitor.
Bilastine	Bilastine may be increased by P-glycoprotein/ABCB1 inhibitors. Patients with severe or moderate renal impairment who are on p-glycoprotein inhibitors should consider other options.
Colchicine	The serum Colchicine concentration may be increased by P-glycoprotein/ABCB1 inhibitors. The distribution of Colchicine into specific tissues, such as the brain, may be increased. Patients with impaired renal and hepatic function, who are also taking a p-glycoprotein inhibitor, should not be given colchicine. Reduce the dose of colchicine for those with normal renal or hepatic function. See full monograph for details.
Moderate CYP2D6 inhibitors	Eliglustat serum concentration may increase Management: Lower the daily eliglustat dose by 84 mg. Use eliglustat only in combination with a mild CYP2D6 inhibitor or a strong/moderate CYP3A4 inhibitor.
Strong CYP2D6 inhibitors	Eliglustat serum concentration may increase Management: Lower the daily eliglustat dose by 84 mg. Use eliglustat only in combination with a strong CYP2D6 inhibitor and a strong, moderate or strong CYP3A4 inhibitor.
Moderate CYP3A4 inhibitors	Eliglustat serum concentration may increase Under certain circumstances, Eliglustat should not be used. For more information, please refer to the full drug interaction monograph.
Strong CYP3A4 inhibitors	Eliglustat serum concentration may increase Under certain circumstances, Eliglustat should not be used. For more information, please refer to the full drug interaction monograph.
Dabigatran Etexilate	The serum concentrations may be increased by P-glycoprotein/ABCB1 inhibitors. Treatment: Dabigatran dosage reductions may be necessary. Particular recommendations can vary depending on the labeling of the US and Canada, specific Pgp inhibitors, renal function, indications for dabigatran therapy, and other factors. Refer to the full monograph and dabigatran labeling.
Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Dacomitinib	High risk of Inhibitors causing an increase in serum concentrations of CYP2D6 substrates. Management: Do not use dacomitinib concurrently with CYP2D6 Substrates that have a narrow therapeutic Index.
Digoxin	The serum Digoxin concentration may be increased by Eliglustat. Treatment: Before initiating eliglustat, take digoxin serum levels from patients who are taking digoxin. Reduce digoxin doses 30% before eliglustat initiation. Continue monitoring.
DOXOrubicin (Conventional)	P-glycoprotein/ABCB1 inhibitors may increase serum levels of DOXOrubicin (Conventional). Treatment: If you are treated with doxorubicin, consider alternative P-glycoprotein inhibitors. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc.
Edoxaban	The serum concentrations of Edoxaban may be increased by P-glycoprotein/ABCB1 inhibitors. Management: See full monograph for details. Patients receiving edoxaban to treat venous embolism are advised to take lower doses when taking it with P-gp inhibitors. For patients with atrial fibrillation, edoxaban should not be adjusted in the same way.
Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
Pitolisant	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances.
Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
Venetoclax	Venetoclax may be increased by P-glycoprotein/ABCB1 inhibitors. Treatment: Patients who are concomitantly treated with P-glycoprotein inhibitors (P-gp), should consider a venetoclax dose decrease of at least 50%.
Risk Factor X (Avoid Combination)
Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Strong CYP3A4 Inducers	Eliglustat serum concentration may be decreased
Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Grapefruit Juice	Eliglustat serum concentration may be increased
Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
PAZOPanib	P-glycoprotein/ABCB1 inhibitors may increase serum levels of PAZOPanib.
St John's Wort	Eliglustat serum concentration may be decreased
Topotecan	Topotecan serum concentrations may be increased by P-glycoprotein/ABCB1 inhibitors
VinCRIStine (Liposomal)	The serum VinCRIStine (Liposomal) concentration may be increased by P-glycoprotein/ABCB1 inhibitors

Monitoring parameters:

Adverse Reactions (especially in Poor Metabolizers):

Poor metabolizers may experience more adverse reactions.

Monitoring Parameters:

Complete Blood Count (CBC)
Platelet count
Prothrombin levels
Electrolyte levels
Chitotriosidase levels
Angiotensin-Converting Enzyme (ACE) levels
Tartrate-Resistant Acid Phosphatase (TRAP) levels

Imaging and Tests:

MRI or CT scan to measure liver and spleen volume
Skeletal X-rays
Dual-energy X-ray absorptiometry (DXA) scan
Pulmonary function tests

Hepatic and Renal Function:

Regular monitoring of liver and kidney function

Cardiac Monitoring:

ECG (Electrocardiography)
Echocardiography

Pediatric Patients:

Pediatric patients should be monitored for growth, as per Balwani 2016 study.

How to administer Cerdelga (Eliglustat)?

Eliglustat is taken by mouth.
It can be taken with or without food.
Swallow the capsules whole with water.
Do not crush, dissolve, or open the capsules.
Avoid consuming grapefruit or grapefruit juice while taking eliglustat, as it may interact with the medication.

Mechanism of action of Cerdelga (Eliglustat):

Eliglustat works by blocking an enzyme that's necessary for making glycosphingolipids.
By doing so, it slows down the formation of a specific type of glycosphingolipid called glucosylceramide.
In type 1 Gaucher disease, there's an accumulation of glucosylceramide in the body, which leads to various complications associated with this condition.
Eliglustat helps reduce the buildup of glucosylceramide, which in turn can alleviate some of the specific problems caused by Gaucher disease.

Absorption:

The amount of eliglustat in the bloodstream depends on the patient's CYP2D6 phenotype.
Poor metabolizers (PMs) may have up to 9 times higher systemic exposure compared to extensive metabolizers (EMs).

Distribution: