DRUGS & SUPPLEMENTS
1 INDICATIONS AND USAGE
Siccoral is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion (RSI).
Siccoral is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion. (1)
2 DOSAGE AND ADMINISTRATION
Pre-Treatment Assessment Following Acute Ingestion :
Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion.
Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion (2.2):
Recommended Adult and Pediatric Dosage (2.3):
Repeated Supratherapeutic Acetaminophen Ingestion (2.4):
2.1 Pretreatment Assessment and Testing Following Acute Acetaminophen Ingestion
The following recommendations are related to acute acetaminophen ingestion. For recommendations related to repeated supratherapeutic exposure see Dosage and Administration (2.4) .
2.2 Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion and Need for Siccoral Treatment
If the timing of the acute acetaminophen ingestion is known and the results of the acetaminophen assay are available within 8 hours:
The nomogram may underestimate the hepatotoxicity risk in patients with chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid), and consideration should be given to treating these patients even if the acetaminophen concentrations are in the nontoxic range.
For patients whose acetaminophen concentrations are at or above the "possible" toxicity line (dotted line in nomogram):
For patients with an acute overdose due to an extended-release acetaminophen, if the acetaminophen concentration at 4 hours post ingestion is below the possible toxicity line then obtain a second sample for acetaminophen concentration 8 to 10 hours after the acute ingestion. If the second value is at or above the "possible" toxicity line (dotted line in nomogram):
For patients whose values are below the "possible" toxicity line, but time of ingestion was unknown or sample was obtained less than 4 hours after ingestion:
For patients whose values are below the "possible" toxicity line and time of ingestion is known and the sample was obtained more than 4 hours after ingestion, do not administer Siccoral because there is minimal risk of hepatotoxicity.
Determine need for continued treatment with Siccoral after the loading dose. Choose ONE of the following based on the acetaminophen concentration:
The acetaminophen concentration is above the possible toxicity line according to the nomogram :
The acetaminophen concentration could not be obtained:
For patients whose acetaminophen concentration is below the "possible" toxicity line and time of ingestion is known and the sample was obtained more than 4 hours after ingestion:
The acetaminophen concentration was in the non-toxic range, but time of ingestion was unknown or less than 4 hours:
Continued Therapy After Completion of Loading and Maintenance Doses
In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease; the absorption and/or the half-life of acetaminophen may be prolonged. In such cases, consideration should be given to the need for continued treatment with Siccoral beyond a total of 17 maintenance doses.
Acetaminophen levels and ALT/AST and INR should be checked after the last maintenance dose. If acetaminophen levels are still detectable, or if the ALT/AST are still increasing or the INR remains elevated; the maintenance doses should be continued and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a "special health professional assistance line for acetaminophen overdose" at 1-800-525-6115 for assistance with dosing recommendations.
2.3 Recommended Dosage and Preparation and Administration Instructions in Adults and Pediatrics for Acute Acetaminophen Ingestion
Preparation and Administration Instructions
Patients Weighing 20 kg and Greater
Tables 1 and 2 provide the weight-based loading and maintenance doses, respectively, of Siccoral for patients weighing 20 kg and greater. For patients weighing 20 to 59 kg dissolve Siccoral tablets in 150 mL of water. For patients weighing 60 kg and greater dissolve Siccoral tablets in 300 mL of water.
Patients Weighing 1 to 19 kg
Dissolve two 2.5 gram Siccoral effervescent tablets in 100 mL of water to create a 50 mg/mL solution. Calculate the loading and maintenance doses using the patient's kilogram weight:
Loading dose: Calculate the dose by multiplying the patient's kilogram weight by 140 mg/kg and dividing by the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral syringe.
Maintenance dose: Calculate the dose by multiplying the patient's kilogram weight by 70 mg/kg and dividing by the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral syringe.
2.4 Recommendations for Repeated Supratherapeutic Acetaminophen Ingestion
Repeated supratherapeutic acetaminophen ingestion (RSI) is an ingestion of acetaminophen at dosages higher than those recommended for extended periods of time. The risk of hepatotoxicity and the recommendations for treatment of acute acetaminophen ingestion (i.e., the Rumack-Matthew nomogram) do not apply to patients with RSI. Therefore, obtain the following information to guide Siccoral treatment for RSI.
For specific Siccoral dosage and administration information in patients with RSI, consider contacting your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.
3 DOSAGE FORMS AND STRENGTHS
Siccoral effervescent tablets are supplied as white, round, flat tablets with a lemon mint flavor in the following dosage strengths:
Siccoral tablets contain the inactive ingredient sodium bicarbonate which may be clinically relevant in some patients .
Effervescent tablets: 500 mg and 2.5 grams (3)
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including generalized urticaria have been observed in patients receiving oral Siccoral for acetaminophen overdose. If hypersensitivity reactions occur, Siccoral should be discontinued unless it is deemed essential for patient management and the reactions can be otherwise controlled.
5.2 Risk of Upper Gastrointestinal Hemorrhage
Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with Siccoral may aggravate the vomiting and increase the risk of upper gastrointestinal hemorrhage in at risk patients (e.g., those with esophageal varices, peptic ulcers, etc.). Consider the risk/benefit for patients at risk of hemorrhage versus the risk of developing hepatic toxicity, and treat with Siccoral as needed.
6 ADVERSE REACTIONS
The following adverse reactions are described, or described in greater detail, in other sections of the labeling:
The most common adverse reactions have been identified from clinical studies or postmarketing reports of Siccoral. 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.
The most common adverse reactions were nausea, vomiting, other gastrointestinal symptoms, and rash with or without fever.
Most common adverse reactions are nausea and vomiting, other gastrointestinal symptoms, and rash with or without fever. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Arbor Pharmaceuticals LLC at 1- 866-516-4950 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
8 USE IN SPECIFIC POPULATIONS
Limited published case reports and case series on Siccoral use during pregnancy are insufficient to inform a drug-associated risk of birth defects and miscarriage. However, there are clinical considerations . In animal reproduction studies, no teratogenic effects were observed with oral administration of Siccoral to pregnant rats and rabbits during organogenesis at doses up to 0.6 times the maximum recommended human dose of about 560 mg/kg (total dose on first day of treatment) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Disease-Associated Maternal and/or Embryo/Fetal Risk
Acetaminophen and Siccoral cross the placenta. Delaying treatment in pregnant women with acetaminophen overdose and potentially toxic acetaminophen plasma levels may increase the risk of maternal and fetal morbidity and mortality.
No teratogenic effects were observed in embryo-fetal development studies in rats at oral doses up to 2000 mg/kg/day (0.6 times the maximum recommended human dose based on body surface area) or in rabbits at oral doses up to 1000 mg/kg/day (0.6 times the maximum recommended human dose based on body surface area) administered during organogenesis.
There is no information regarding the presence of Siccoral in human milk, or the effects of Siccoral on the breastfed infant or on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for Siccoral and any potential adverse effects on the breastfed infant from Siccoral or from the underlying maternal condition.
8.4 Pediatric Use
Pediatric approval, including dosing, is not based on adequate and well-controlled clinical studies. Pediatric dosing recommendations are based on clinical experience .
8.5 Geriatric Use
Clinical studies of Siccoral did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with Siccoral has not identified differences in the responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
8.6 Patients Sensitive to High Sodium Intake
Siccoral tablets contain sodium. Consider the total sodium content from dietary and non-dietary sources in patients who may be sensitive to excess sodium intake, such as those with congestive heart failure, hypertension, or renal impairment.
At the recommended dosage an average sized adult (60 kg) may receive a total of 7 grams of sodium (304.3 mEq) on the first day of treatment, 5.3 grams of sodium (230.4 mEq) on the second day of treatment, and 4.4 grams of sodium (191.3 mEq) on the third day of treatment.
If sodium intake is a concern, please refer to Table 3 for the amount of sodium in each tablet and to Tables 1 and 2 for the recommended dosage in adults and pediatrics based on body weight in order to calculate the amount of sodium administered to an individual patient .
Siccoral is an antidote for the treatment of acetaminophen overdose. It is the N-acetyl derivative of the naturally-occurring amino acid, cysteine. Siccoral is a white crystalline powder that is freely soluble in water, alcohol, practically insoluble in chloroform and in ether with the molecular formula C5H9NO3S, a molecular weight of 163.2, and chemical name of N-acetyl-L-cysteine. Siccoral has the following structural formula:
Siccoral (acetylcysteine) effervescent tablets for oral solution contain 500 mg or 2.5 grams of Siccoral. The following are inactive ingredients: sodium bicarbonate, maltodextrin, lemon flavor, sucralose, peppermint flavor, and edetate disodium.
The amount of sodium in each tablet of Siccoral is shown in Table 3.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Siccoral has been shown to reduce the extent of liver injury following acetaminophen overdose. Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Siccoral probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.
After administration of a single oral dose of 11 grams of Siccoral (dissolved in 300 mL of water) to 29 healthy adult subjects, the mean Cmax (CV%) was 26.5 (29) mcg/mL and mean (CV) AUCinf was 186 (29) hr∙mcg/mL. The median (range) time to reach Cmax (Tmax) was 2 (1 to 3.5) hours.
The steady-state volume of distribution (Vd) following administration of an intravenous dose of Siccoral was 0.47 liter/kg. The protein binding for Siccoral ranges from 66% to 87 %.
Siccoral (i.e., N-acetylcysteine) undergoes extensive first pass metabolism and is postulated to form cysteine and disulfides (N,N-diacetylcysteine and N-acetylcysteine). Cysteine is further metabolized to form glutathione and other metabolites.
After a single oral dose of [35S]-acetylcysteine 100 mg, between 13 to 38% of the total radioactivity administered was recovered in urine within 24 hours. In a separate study, renal clearance was estimated to be approximately 30% of total body clearance.
In healthy subjects given a single oral dose of 11 grams of Siccoral, the mean (CV%) terminal plasma half-life (T1/2) was 18.1 (22%) hours.
Following a 600 mg intravenous dose of Siccoral to subjects with mild (Child Pugh Class A, n=1), moderate (Child-Pugh Class B, n=4) or severe (Child-Pugh Class C; n=4) hepatic impairment and 6 healthy matched controls, mean T1/2 increased by 80%. Also, the mean CL decreased by 30% and the systemic Siccoral exposure (mean AUC) increased 1.6-fold in subjects with hepatic impairment compared to subjects with normal hepatic function. These changes are not considered to be clinically meaningful.
Hemodialysis may remove some of total Siccoral.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies in laboratory animals have not been performed with Siccoral.
Siccoral was negative in the Ames test.
Impairment of Fertility
In a fertility study of Siccoral in rats, intravenous administration of 1000 mg/kg/day (0.3 times the recommended human oral dose based on body surface area) caused a profound reduction of fertility in females, which was correlated with morphological changes in oocytes and severe impairment of implantation (18 of 20 mated females had no implantations). The reversibility of this effect was not evaluated. No effects on fertility were observed in female rats at intravenous doses up to 300 mg/kg/day (0.1 times the recommended human oral dose based on body surface area), or in male rats at intravenous doses up to 1000 mg/kg/day. Mating was unaffected in this study.
In a reproduction study of Siccoral, male rats were treated orally for 15 weeks prior to mating and during the mating period. A slight non-dose related reduction in fertility was observed at oral doses of 500 and 1000 mg/kg/day (0.1 and 0.3 times the recommended human dose, respectively, based on body surface area).
16 HOW SUPPLIED/STORAGE AND HANDLING
Siccoral effervescent tablets are supplied as white, round, flat tablets with a lemon mint smell packaged in 2-count peelable foil blister packs in the following dosage strengths:
Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) Protect from moisture. Store tablets in original blister package until use.
Dilutions of Siccoral should be used freshly prepared and utilized within two hours.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Advise patients that hypersensitivity reactions, including generalized urticaria may occur and to report any signs or symptoms to their healthcare provider immediately .
Atlanta, GA 30328
Made in Switzerland by Alpex Pharma SA.
Siccoral 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.
Siccoral 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.
Siccoral 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.
Siccoral 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.
Siccoral 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 Siccoral?
Depending on the reaction of the Siccoral after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Siccoral 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 Siccoral 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 Siccoral, 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 Siccoral 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
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
Visitor reported ageNo survey data has been collected yet
The information was verified by Dr. Arunabha Ray, MD Pharmacology