DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Radicut is indicated for the treatment of amyotrophic lateral sclerosis (ALS).
Radicut is indicated for the treatment of amyotrophic lateral sclerosis (ALS) (1)
2 DOSAGE AND ADMINISTRATION
The recommended dosage is 60 mg administered as an intravenous infusion over 60 minutes as follows:
2.1 Dosage Information
2.2 Preparation and Administration Information
Radicut is for intravenous infusion only.
Do not use if the oxygen indicator has turned blue or purple before opening the package [see How Supplied/Storage and Handling (16.1, 16.2) ]. Once the overwrap package is opened, use within 24 hours [see Storage and Handling (16.2) ].
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administer each 60 mg dose of Radicut injection as two consecutive 30 mg intravenous infusion bags over a total of 60 minutes (infusion rate approximately 1 mg per minute [3.33 mL per minute]).
Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction [ see Warnings and Precautions (5.1, 5.2) ].
Other medications should not be injected into the infusion bag or mixed with Radicut.
3 DOSAGE FORMS AND STRENGTHS
Radicut is supplied for intravenous infusion in a single-dose polypropylene bag containing 30 mg of Radicut in 100 mL of clear, colorless aqueous solution.
Radicut is contraindicated in patients with a history of hypersensitivity to Radicut or any of the inactive ingredients of this product. Hypersensitivity reactions and anaphylactic reactions have occurred .
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have been reported in spontaneous postmarketing reports with Radicut.
Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue Radicut, treat per standard of care, and monitor until the condition resolves .
5.2 Sulfite Allergic Reactions
Radicut contains sodium bisulfite, a sulfite that may cause allergic type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity occurs more frequently in asthmatic people.
6 ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling:
Most common adverse reactions (at least 10% and greater than placebo) are contusion, gait disturbance, and headache, (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Mitsubishi Tanabe Pharma America, Inc. at 1-888-292-0058 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In randomized, placebo-controlled trials, 184 ALS patients were administered Radicut 60 mg in treatment cycles for 6 months. The population consisted of Japanese patients who had a median age of 60 years (range 29-75) and were 59% male. Most (93%) of these patients were living independently at the time of screening.
Most Common Adverse Reactions Observed During Clinical Studies
Table 1 lists the adverse reactions that occurred in ≥ 2% of patients in the RADICAVA-treated group and that occurred at least 2% more frequently than in the placebo-treated group in randomized placebo-controlled ALS trials. The most common adverse reactions that occurred in ≥10% of RADICAVA-treated patients were contusion, gait disturbance, and headache.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Radicut outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and subcutaneous tissue disorders: Hypersensitivity reactions and anaphylaxis.
8 USE IN SPECIFIC POPULATIONS
There are no adequate data on the developmental risk associated with the use of Radicut in pregnant women. In animal studies, administration of Radicut to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. Most of these effects occurred at doses that were also associated with maternal toxicity (see Animal Data).
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk for major birth defects and miscarriage in patients with ALS is unknown.
In rats, intravenous administration of Radicut (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses. In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring. A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg, on a body surface area (mg/m2) basis.
In rabbits, intravenous administration of Radicut (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) on a body surface area (mg/m2) basis.
The effects on offspring of Radicut (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested. Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m2 basis.
There are no data on the presence of Radicut in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Radicut and its metabolites are excreted in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Radicut and any potential adverse effects on the breastfed infant from Radicut or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness of Radicut in pediatric patients have not been established.
8.5 Geriatric Use
Of the 184 patients with ALS who received Radicut in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
8.6 Renal Impairment
The effect of renal impairment on the pharmacokinetics of Radicut has not been studied. However, renal impairment is not expected to significantly affect the exposure to Radicut. No dose adjustment is needed in these patients.
8.7 Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of Radicut has not been studied. No dose adjustment is needed for patients with mild or moderate hepatic impairment. No specific dosing recommendation can be provided for patients with severe hepatic impairment.
The active ingredient in Radicut is Radicut, which is a member of the substituted 2-pyrazolin-5-one class. The chemical name of Radicut is [3-methyl-1-phenyl-2-pyrazolin-5-one]. The molecular formula is C10H10N2O and the molecular weight is 174.20.
The chemical structure is:
Radicut is a white crystalline powder with a melting point of 129.7°C. It is freely soluble in acetic acid, methanol, or ethanol and slightly soluble in water or diethyl ether.
Radicut injection is a clear, colorless liquid provided as a sterile solution.
Radicut injection is supplied for intravenous infusion in a polypropylene bag containing 30 mg Radicut in 100 mL isotonic, sterile, aqueous solution, which is further overwrapped with polyvinyl alcohol (PVA) secondary packaging. The overwrapped package also contains an oxygen absorber and oxygen indicator to minimize oxidation. Each bag contains the following inactive ingredients: L-cysteine hydrochloride hydrate (10 mg), sodium bisulfite (20 mg). Sodium chloride is added for isotonicity and phosphoric acid and sodium hydroxide are added to adjust to pH 4.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The mechanism by which Radicut exerts its therapeutic effect in patients with ALS is unknown.
Radicut is administered by IV infusion. The maximum plasma concentration of Radicut was reached by the end of infusion. There was a trend of more than dose-proportional increase in area under the concentration-time curve (AUC) and Cmax of Radicut. With multiple-dose administration, Radicut does not accumulate in plasma.
Radicut is bound to human serum proteins (92%), mainly to albumin, with no concentration dependence in the range of 0.1 to 50 micromol/L.
The mean terminal elimination half-life of Radicut is 4.5 to 6 hours. The half-lives of its metabolites are 2 to 2.8 hours.
Radicut is metabolized to a sulfate conjugate and a glucuronide conjugate, which are not pharmacologically active. The glucuronide conjugation of Radicut involves multiple uridine diphosphate glucuronosyltransferase isoforms (UGT1A6, UGT1A9, UGT2B7, and UGT2B17) in the liver and kidney. In human plasma, Radicut is mainly detected as the sulfate conjugate, which is presumed to be formed by sulfotransferases.
In Japanese and Caucasian healthy volunteer studies, Radicut was excreted mainly in the urine as its glucuronide conjugate form (70-90% of the dose). Approximately 5-10% of the dose was recovered in the urine as sulfate conjugate, and only 1% of the dose or less was recovered in the urine as unchanged form. In vitro studies suggest that sulfate conjugate of Radicut is hydrolyzed back to Radicut, which is then converted to the glucuronide conjugate in the human kidney before excretion into the urine.
No age effect on Radicut pharmacokinetics has been found [see Use in Specific Populations ].
Patients with Renal and Hepatic Impairment
No pharmacokinetic data are available in patients with renal impairment or hepatic impairment [see Use in Specific Populations (8.6, 8.7) ].
Male and Female Patients
No gender effect on Radicut pharmacokinetics has been found.
Racial or Ethnic Groups
There were no significant racial differences in Cmax and AUC of Radicut between Japanese and Caucasian subjects.
Drug Interaction Studies
The pharmacokinetics of Radicut is not expected to be significantly affected by inhibitors of CYP enzymes, UGTs, or major transporters.
In vitro studies demonstrated that, at clinical dose, Radicut and its metabolites are not expected to significantly inhibit cytochrome P450 enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4), UGT1A1, UGT2B7, or transporters (P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, and OCT2) in humans. Radicut and its metabolites are not expected to induce CYP1A2, CYP2B6, or CYP3A4 at the clinical dose level of Radicut.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of Radicut has not been adequately assessed.
Radicut was negative in in vitro and in vivo (mouse micronucleus) assays.
Impairment of Fertility
Intravenous administration of Radicut (0, 3, 20, or 200 mg/kg) prior to and throughout mating in males and females and continuing in females to gestation day 7 had no effect on fertility; however, disruption of the estrus cycle and mating behavior was observed at the highest dose tested. No effects on reproductive function were observed at the lower doses, which are up to 3 times the RHD of 60 mg, on a body surface area (mg/m2) basis.
14 CLINICAL STUDIES
The efficacy of Radicut for the treatment of ALS was established in a 6-month, randomized, placebo-controlled, double-blind study conducted in Japanese patients with ALS who were living independently and met the following criteria at screening:
The study enrolled 69 patients in the Radicut arm and 68 in the placebo arm. Baseline characteristics were similar between these groups, with over 90% of patients in each group being treated with riluzole.
Radicut was administered as an intravenous infusion of 60 mg given over a 60 minute period according to the following schedule:
The primary efficacy endpoint was a comparison of the change between treatment arms in the ALSFRS-R total scores from baseline to Week 24. The ALSFRS-R scale consists of 12 questions that evaluate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS (speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency). Each item is scored from 0-4, with higher scores representing greater functional ability. The decline in ALSFRS-R scores from baseline was significantly less in the RADICAVA-treated patients as compared to placebo. The distribution of change in ALSFRS-R scores from baseline to Week 24 by percent of patients is shown in Figure 1.
Figure 1: Distribution of Change from Baseline to Week 24 in ALSFRS-R Scores
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
Radicut injection is supplied as a 30 mg/100 mL clear, colorless, sterile solution for intravenous infusion in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels . These are supplied in cartons as listed below.
16.2 Storage and Handling
Store at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F). Protect from light. Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours.
17 PATIENT COUNSELING INFORMATION
Advise the patients to read the FDA-approved patient labeling (Patient Information).
Advise patients to seek immediate medical care if they experience signs or symptoms of a hypersensitivity reaction .
Sulfite Allergic Reactions
Advise patients about potential for sulfite sensitivity. Inform patients that Radicut contains sodium bisulfite, which may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, and to seek immediate medical care if they experience these signs or symptoms .
Pregnancy and Breastfeeding
Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during Radicut therapy .
Advise patients to notify their healthcare provider if they intend to breastfeed or are breastfeeding an infant .
Marketed and distributed by:
Mitsubishi Tanabe Pharma America, Inc., a US subsidiary of Mitsubishi Tanabe Pharma Corporation
525 Washington Blvd., Suite 400,
Jersey City, NJ 07310
Radicut is a trademark of Mitsubishi Tanabe Pharma Corporation
© Mitsubishi Tanabe Pharma Corporation 
118839 [08/2017] Iss. 08/17
Radicut (ra di ká vah)
for intravenous infusion
Radicut pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Radicut available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Radicut destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Radicut Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Radicut pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Radicut?
Depending on the reaction of the Radicut after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Radicut not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Radicut addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Radicut, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Radicut consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
One visitor reported side effectsDid you get side effects while taking the Radicut drug, or were there no side effects?
According to the survey conducted by website sdrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Radicut medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
One visitor reported price estimatesWhat is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sdrugs.com website users shows the following figures about several people who felt the medicine Radicut is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
One visitor reported frequency of useHow often in a day do you take the medicine?
Are you taking the Radicut drug as prescribed by the doctor?
Few medications can be taken Once in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sdrugs.com website users about the frequency of taking the drug Radicut is mentioned below.
Eight visitors reported dosesWhat is the dose of Radicut drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 11-50mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
One visitor reported time for resultsWhat is the time duration Radicut drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 2 weeks to notice the result from using Radicut drug. The time needed to show improvement in health condition after using the medicine Radicut need not be same for all the users. It varies based on other factors.
Visitor reported administrationNo survey data has been collected yet
Five visitors reported age
The information was verified by Dr. Arunabha Ray, MD Pharmacology