Exservan (riluzole)
Amyotrophic Lateral Sclerosis Agents - Anti-glutamatergics Oral Film, Medicated (Ea)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Riluzole is an antiglutamate agent that acts in the CNS.
Riluzole, a synthetic aryl-substituted benzothiazolamine, is an antiglutamate agent that acts in the CNS. It has been suggested that the motor neuron degeneration associated with amyotrophic lateral sclerosis (ALS) may be related to accumulation of excitatory amino acids (EAAs), principally glutamate, at synapses in the CNS and resultant ''excitotoxicity'' and cell death.
The precise mechanism of action of riluzole in patients with ALS has not been fully elucidated but appears to involve interference with the effects mediated by EAAs in the CNS, possibly through inhibition of glutamic acid release, blockade or inactivation of voltage-dependent sodium channels, and/or activation of a G-protein-dependent signal transduction pathway. While some data also suggest that riluzole may act via noncompetitive blockade of EAA receptors, the drug has not been shown to bind to any known glutamate receptor. Riluzole has exhibited neuroprotective properties in vitro and in vivo in animals, including inhibition of neuronal toxicity associated with exposure to EAAs or cerebrospinal fluid from ALS patients, and inhibition of neuronal toxicity associated with anoxia or focal or global ischemia.
Riluzole prolonged survival in a study in a transgenic mouse model of ALS but did not delay onset of the disease.
Riluzole exhibits dose-proportional pharmacokinetics over the dosage range of 25-100 mg every 12 hours. The oral bioavailability of the drug is approximately 60%. Similar pharmacokinetics were observed following intragastric administration (via feeding tube) and oral administration of the oral suspension under fasting conditions.
Administration of riluzole with food decreases AUC by 20% and peak plasma concentrations by 45%. Riluzole is 96% bound to plasma proteins, principally to albumin and lipoproteins. The drug is metabolized by cytochrome P-450 (CYP) 1A2 and by direct and sequential glucuronidation; some metabolites appear to be active in vitro, but the clinical importance is not known.
At least 88% of a dose is metabolized; 90% is excreted in urine (only 2% as unchanged drug) and 5% is excreted in feces. The half-life of riluzole is 12 hours.
USES: This medication is used to treat a certain type of nerve disease called amyotrophic lateral sclerosis (ALS, also commonly called Lou Gehrig's disease). Riluzole helps to slow down the worsening of this disease and prolong survival.
Generic name: riluzole
Pronunciation: (RIL-ue-zole)
Drug class: Amyotrophic Lateral Sclerosis Agents - Anti-glutamatergics
Therapeutic class: Locomotor System
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Exservan
Indications
The following indications are listed for Exservan:
- Amyotrophic Lateral Sclerosis
Dosing
For the management of amyotrophic lateral sclerosis (ALS), the recommended dosage of riluzole is 50 mg twice daily. Higher daily dosages have not been shown to provide any additional benefit but may increase the risk of adverse effects.
Riluzole is administered orally twice daily (as tablets or oral suspension). Because food decreases oral bioavailability of the drug, the manufacturer recommends that riluzole be taken in a fasting state (e.g., 1 hour before or 2 hours after a meal).
Store riluzole tablets at 20-25degreesC and protect from bright light. Store the oral suspension upright at 20-25degreesC (excursions permitted to 15-30degreesC); protect from bright light and do not freeze. Use the oral suspension within 15 days of initially opening the bottle.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Exservan 50 Mg Film | Maintenance | Place 1 film (50 mg) on top of tongue, allow to dissolve then swallowby translingual route 2 times per day. |
No dosing information is available for this tab.
Drug interactions
There is no enhanced messaging for this drug.
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Selected Cyp1a2 Substrates/Viloxazine
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Viloxazine is a strong inhibitor of CYP1A2 and may increase the total exposure of sensitive CYP1A2 substrates.(1) The FDA defines strong inhibition as an increase in drug area-under-curve (AUC) greater than 5-fold.(2)
CLINICAL EFFECTS: Concurrent use of viloxazine with drugs primarily metabolized by CYP1A2 may lead to elevated drug levels and increase the risk of adverse reactions associated with the CYP1A2 substrate.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Drugs linked to this monograph are moderately sensitive to CYP1A2 inhibition. Coadministration of viloxazine with moderately sensitive CYP1A2 substrates is not recommended. If coadministered, dose reduction of the CYP1A2 substrate may be warranted.(1)
DISCUSSION: Concomitant use of viloxazine significantly increases the total exposure, but not peak exposure, of sensitive CYP1A2 substrates, which may increase the risk of adverse reactions associated with these CYP1A2 substrates. In a study, viloxazine increased the AUC of caffeine by almost 6-fold.(1) Though not designed to evaluate drug interactions, the open-label portion of a pediatric randomized controlled trial looking at the association of riluzole concentrations with efficacy and adverse effects found that fluvoxamine (a strong CYP1A2 inhibitor) increased riluzole concentrations by about 2-fold.(3) CYP1A2 substrates linked to this monograph include: caffeine and riluzole.(2,4)
There are no moderate interactions for this drug.
Contraindications
*History of severe hypersensitivity reactions to the drug or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
- Disease of liver
- Interstitial lung disease
- Neutropenic disorder
Adverse reactions
The most common adverse effects (>=5% and greater than placebo) with riluzole tablets include asthenia, nausea, dizziness, decreased lung function, and abdominal pain.
The most common adverse effects (>=5% and greater than placebo) with riluzole oral suspension include oral hypoesthesia, asthenia, nausea, decreased lung function, hypertension, and abdominal pain.
More Frequent
- Respiratory depression
Less Frequent
- Apnea
- Dyspnea
- Hypertension
- Increased alanine transaminase
- Pneumonia
- Respiration changes
Rare or Very Rare
- Acute hepatitis
- Anaphylaxis
- Angioedema
- Exfoliative dermatitis
- Facial edema
- Hepatitis
- Hyperbilirubinemia
- Hypersensitivity pneumonitis
- Hypokalemia
- Hyponatremia
- Increased urinary frequency
- Interstitial lung disease
- Necrotizing pancreatitis
- Neutropenic disorder
- Pancreatitis
- Phlebitis
- Seizure disorder
- Tachycardia
More Frequent
- Acute abdominal pain
- Anorexia
- Diarrhea
- Dizziness
- Drowsy
- Flatulence
- General weakness
- Nausea
- Oral hypoesthesia
- Paresthesia
- Tremor
- Vomiting
Less Frequent
- Abnormal hepatic function tests
- Alopecia
- Arthralgia
- Back pain
- Bronchitis
- Constipation
- Cough
- Eczema
- Headache disorder
- Insomnia
- Peripheral edema
- Pruritus of skin
- Rhinitis
- Stomatitis
- Vertigo
- Xerostomia
Rare or Very Rare
- Candidiasis
- Depression
- Dysphagia
- Dysuria
- Hostility
- Malaise
- Tooth disorder
- Urinary tract infection
Precautions
No enhanced messaging available.
Efficacy and safety of riluzole have not been established in pediatric patients.
There are no adequate data to determine whether riluzole is associated with a risk of developmental abnormalities when used during pregnancy. In animal studies, administration of riluzole to pregnant rats and rabbits resulted in adverse developmental effects (e.g., decreased embryofetal/offspring viability, growth, and functional development) at clinically relevant doses.
If riluzole is used during pregnancy, the patient should be advised of the potential risk to the fetus.
It is not known whether riluzole is distributed into human milk. Riluzole or its metabolites have been detected in milk of lactating rats.
Patients should be advised that the potential for serious adverse effects in nursing infants from riluzole is not known.
The manufacturer does not recommend specific dosage adjustments in geriatric patients.
No overall differences in safety and efficacy have been observed in geriatric patients 65 years of age or older compared with younger adults. Age does not appear to have a clinically important effect on the pharmacokinetics of riluzole. However, greater sensitivity in some older individuals cannot be ruled out.
ICD codes
| Code | Type | Description |
|---|---|---|
| Amyotrophic lateral sclerosis | ||
| G12.21 | ICD10CM | Amyotrophic lateral sclerosis |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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