Actions of Simucin in details
Simucin protects against acetaminophen overdose-induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. It does this by producing the glutathione precursor L-cysteine. Glutathione is required to inactivate an intermediate metabolite (N-acetyl-p-benzoquinoneimine or NAPQI) of acetaminophen that is thought to be hepatotoxic. In acetaminophen overdose cases, excessive quantities of this metabolite are formed because the primary metabolic (glucuronide and sulfate conjugation) pathways become saturated. Simucin may act by reducing the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as Simucin may also directly inactivate the metabolite. The mechanisms of action for Simucin’s well-known mucolytic effects are different. In particular, when inhaled, Simucin (and its metabolic byproduct cysteine) exerts its mucolytic action through its free sulfhydryl group, which reduces the disulfide bonds in the mucus matrix and lowers mucus viscosity. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of Simucin is not affected by the presence of DNA. Simucin is also an antioxidant and reduces oxidative stress. Simucin serves as a prodrug to L-cysteine which is a precursor to the biologic antioxidant, glutathione and hence administration of Simucin replenishes glutathione stores. L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of Simucin, mGluR5. Glutathione also modulates the NMDA receptor by acting at the redox site. These effects on glutamate and NMDA signaling appear to explain some of the positive neuropsychotropic effects associated with NAC. Simucin also possesses some anti-inflammatory effects possibly via inhibiting NF-κB through redox activation of the nuclear factor kappa kinases thereby modulating cytokine synthesis.
How should I take Simucin?
Use Simucin only as directed. Do not use more of it and do not use it more often than your doctor ordered. To do so may increase the chance of side effects.
If you are using Simucin at home, make sure you understand exactly how to use it. If you have any questions about this, check with your doctor.
After using Simucin, try to cough up the loosened or thinned mucus. If this does not work, it may have to be suctioned out. This will prevent too much mucus from building up in the lungs. If you have any questions about this, check with your doctor.
Dosing
The dose of Simucin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Simucin. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For inhalation dosage form (solution):
- To thin or dissolve mucus in lung diseases:
- Adults and children—
- 3 to 5 milliliters (mL) of a 20% solution or 6 to 10 mL of a 10% solution used in a nebulizer three or four times a day. The medicine is inhaled through a face mask, mouthpiece, or tracheostomy.
- The 10 or 20% solution may be used for inhalation as a heavy mist in a tent or croupette.
- Sometimes the 10 or 20% solution is placed directly into the trachea or through a catheter into the trachea for certain conditions.
- Adults and children—
- For use in tests to diagnose lung problems:
- Adults and children—1 to 2 mL of a 20% solution or 2 to 4 mL of a 10% solution used for inhalation or placed directly into the trachea two or three times before the test.
- To thin or dissolve mucus in lung diseases:
Missed Dose
If you miss a dose of Simucin, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
Storage
Store in the refrigerator. Do not freeze.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Store unopened vials of Simucin in the refrigerator. Do not freeze. An open vial of medicine must be used right away.
The opened container should be discarded after 4 days.
Simucin administration
Inhalation: Simucin is incompatible with tetracyclines, erythromycin, amphotericin B, iodized oil, chymotrypsin, trypsin, and hydrogen peroxide. Administer separately. Intermittent aerosol treatments are commonly given when patient arises, before meals, and just before retiring at bedtime.
Oral:
Effervescent tablets (Simucin): Use within 2 hours of preparation. If the patient vomits within 1 hour of administration, repeat that dose. If the patient is persistently unable to retain the orally administered Simucin, Simucin may be administered by nasoduodenal tube. An intravenous formulation of Simucin may also be considered.
Solution for oral administration: For the treatment of acetaminophen overdose, administer orally as a 5% solution. Use within 1 hour of preparation. The unpleasant odor (sulfur-like) becomes less noticeable as treatment progresses. If patient vomits within 1 hour of dose, readminister. (Note: It is helpful to put the Simucin on ice, in a cup with a cover, and drink through a straw; alternatively, administer via an NG tube).
IV (Acetadote): Acetaminophen overdose:
Loading dose: Administer over 1 hour.
Second dose: Administer over 4 hours.
Third dose: Administer over 16 hours.
If the commercial IV form is unavailable, the solution for inhalation has been used; each dose should be infused through a 0.2 micron Millipore filter (in-line) over 60 minutes (Yip 1998); intravenous administration of the solution for inhalation is not USP 797-compliant.
Alternative recommendations (off-label):
"Two bag method" (off-label dosing): Administer first dose (200 mg/kg) over 4 hours, then administer the second dose (100 mg/kg) over 16 hours (Wong 2016b).
"Single bag method" (off-label dosing): Administer initial dose (150 mg/kg) over 60 minutes, then decrease the rate and administer the remaining dose (14 mg/kg/hour) over 20 hours (Johnson 2011). Note: Patients weighing >69 kg will require a second bag to complete the dosing regimen.
Simucin pharmacology
Mechanism of Action
Simucin 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. Simucin 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.
Pharmacokinetics
Absorption
After administration of a single oral dose of 11 grams of Simucin (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.
Distribution
The steady-state volume of distribution (Vd) following administration of an intravenous dose of Simucin was 0.47 liter/kg. The protein binding for Simucin ranges from 66% to 87 %.
Elimination
Metabolism
Simucin (i.e., Simucin) undergoes extensive first pass metabolism and is postulated to form cysteine and disulfides (N,N-diacetylcysteine and Simucin). Cysteine is further metabolized to form glutathione and other metabolites.
Excretion
After a single oral dose of [35S]-Simucin 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 Simucin, the mean (CV%) terminal plasma half-life (T1/2) was 18.1 (22%) hours.
Specific Populations
Hepatic Impairment
Following a 600 mg intravenous dose of Simucin 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 Simucin 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.
Renal Impairment
Hemodialysis may remove some of total Simucin.
Reviews
The results of a survey conducted on ndrugs.com for Simucin are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Simucin. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
