Consists of Codeine, Paracetamol
Actions of Codeine (Comfarol) in details
Codeine (Comfarol) Sulfate is an opioid analgesic, related to morphine, but with less potent analgesic properties. Codeine (Comfarol) is selective for the mu receptor, but with a much weaker affinity than morphine. The analgesic properties of Codeine (Comfarol) have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.
Effects of the Central Nervous System (CNS)
The principal therapeutic action of Codeine (Comfarol) Sulfate is analgesia. Although the precise mechanism of the analgesic action is unknown, specific CNS opiate receptors and endogenous compounds with morphine-like activity have been identified throughout the brain and spinal cord and are likely to play a role in the expression and perception of analgesic effects. Some other CNS effects of Codeine (Comfarol) include anxiolysis, euphoria, and feelings of relaxation. Codeine (Comfarol) Sulfate causes respiratory depression, in part by a direct effect on the brainstem respiratory centers. Codeine (Comfarol) Sulfate and other related opioids depress the cough reflex by direct effect on the cough center in the medulla. Codeine (Comfarol) Sulfate may also cause miosis.
Effects on the Gastrointestinal Tract and on Other Smooth Muscle
Gastric, biliary and pancreatic secretions may be decreased by Codeine (Comfarol). Codeine (Comfarol) also causes a reduction in motility and is associated with an increase in tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm. The end result may be constipation. Codeine (Comfarol) can cause a marked increase in biliary tract pressure as a result of the spasm of the sphincter of Oddi. Codeine (Comfarol) may also cause spasms of the sphincter of the urinary bladder.
Effects on the Cardiovascular System
Codeine (Comfarol) produces peripheral vasodilation which may result in orthostatic hypotension and fainting. Release of histamine can occur, which may play a role in opioid-induced hypotension. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, and sweating.
Endocrine System
Opioid agonists such as Codeine (Comfarol) Sulfate have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagons in humans and other species, rats and dogs. Thyroid stimulating hormone (TSH) has been shown to be both inhibited and stimulated by opioids.
Immune System
Codeine (Comfarol) has been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.
How should I take Codeine (Comfarol)?
Follow all directions on your prescription label. Codeine (Comfarol) can slow or stop your breathing. Never use Codeine (Comfarol) in larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems to stop working as well in relieving your pain.
Codeine (Comfarol) may be habit-forming, even at regular doses. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. MISUSE OF NARCOTIC MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription. Selling or giving away Codeine (Comfarol) is against the law.
Take Codeine (Comfarol) with food or milk if it upsets your stomach.
Measure liquid medicine with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.
Drink 6 to 8 full glasses of water daily to help prevent constipation while you are taking Codeine (Comfarol). Do not use a stool softener (laxative) without first asking your doctor.
Do not stop using Codeine (Comfarol) suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using Codeine (Comfarol).
Store at room temperature away from moisture and heat.
Keep track of the amount of medicine used from each new bottle. Codeine (Comfarol) is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.
After you have stopped using this medication, flush any unused pills down the toilet. Disposal of medicines by flushing is recommended to reduce the danger of accidental overdose causing death. This advice applies to a very small number of medicines only. The FDA, working with the manufacturer, has determined this method to be the most appropriate route of disposal and presents the least risk to human safety.
Codeine (Comfarol) administration
Oral:
Oral solution [Canadian product]: Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Controlled-release tablets: Codeine (Comfarol) Contin [Canadian product]: Tablets should be swallowed whole; do not chew, dissolve, or crush. All strengths may be halved, except the 50 mg tablets; half tablets should also be swallowed intact.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation (tablet or oral suspension).
Injection [Canadian product]: May be administered by IM or SubQ injection.
Codeine (Comfarol) pharmacology
Mechanism of Action
Codeine (Comfarol) is an opioid agonist, related to morphine, but with less potent analgesic properties. Codeine (Comfarol) is selective for the mu receptor, but with a much weaker affinity than morphine. The analgesic properties of Codeine (Comfarol) have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.
Effects of the Central Nervous System (CNS): The principal therapeutic action of Codeine (Comfarol) is analgesia. Although the precise mechanism of the analgesic action is unknown, specific CNS opiate receptors and endogenous compounds with morphine-like activity have been identified throughout the brain and spinal cord and are likely to play a role in the expression and perception of analgesic effects. Other CNS effects of Codeine (Comfarol) include anxiolysis, euphoria, and feelings of relaxation. Codeine (Comfarol) causes respiratory depression, in part by a direct effect on the brainstem respiratory centers. Codeine (Comfarol) and other related opioids depress the cough reflex by direct effect on the cough center in the medulla. Codeine (Comfarol) may also cause miosis.
Effects on the Gastrointestinal Tract and on Other Smooth Muscle: Gastric, biliary and pancreatic secretions may be decreased by Codeine (Comfarol). Codeine (Comfarol) also causes a reduction in motility and is associated with an increase in tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm. The end result may be constipation. Codeine (Comfarol) can cause a marked increase in biliary tract pressure as a result of the spasm of the sphincter of Oddi. Codeine (Comfarol) may also cause spasms of the sphincter of the urinary bladder.
Effects on the Cardiovascular System: In therapeutic doses, Codeine (Comfarol) does not usually exert major effects on the cardiovascular system. Codeine (Comfarol) produces peripheral vasodilation which may result in orthostatic hypotension and fainting. Release of histamine can occur, which may play a role in opioid-induced hypotension. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, and sweating.
Endocrine System: Opioid agonists have been shown to have a variety of effects on the secretion of hormones. Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagons in humans and other species, rats and dogs. Thyroid stimulating hormone (TSH) has been shown to be both inhibited and stimulated by opioids.
Immune System: Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.
Pharmacodynamics
Codeine (Comfarol) plasma concentrations do not correlate with Codeine (Comfarol) brain concentrations or relief of pain.
The minimum effective concentration varies widely and is influenced by a variety of factors, including the extent of previous opioid use, age and general medical condition. Effective doses in tolerant patients may be significantly higher than in opioid-naïve patients.
Pharmacokinetics
Absorption: Codeine (Comfarol), when administered as Codeine (Comfarol) sulfate, is absorbed from the gastrointestinal tract with maximum plasma concentration occurring 60 minutes post administration.
Food Effects: When 60 mg Codeine (Comfarol) sulfate was administered 30 minutes after ingesting a high fat/high calorie meal, there was no significant change in the rate and extent of absorption of Codeine (Comfarol).
Steady-state: Administration of 15 mg Codeine (Comfarol) sulfate every four hours for 5 days resulted in steady-state concentrations of Codeine (Comfarol), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours.
Distribution: Codeine (Comfarol) has been reported to have an apparent volume of distribution of approximately 3-6 L/kg, indicating extensive distribution of the drug into tissues. Codeine (Comfarol) has low plasma protein binding with about 7-25% of Codeine (Comfarol) bound to plasma proteins.
Metabolism: About 70-80% of the administered dose of Codeine (Comfarol) is metabolized by conjugation with glucuronic acid to Codeine (Comfarol)-6-glucuronide (C6G, about 60%) and via O-demethylation to morphine (about 5-10%) and N-demethylation to norcodeine (about 10%) respectively. UDP-glucuronosyltransferase (UGT) 2B7 and 2B4 are the major enzymes mediating glucurodination of Codeine (Comfarol) to C6G. Cytochrome P450 2D6 is the major enzyme responsible for conversion of Codeine (Comfarol) to morphine (about 5-10%) and P450 3A4 is the major enzyme mediating conversion of Codeine (Comfarol) to norcodeine. Morphine and norcodeine are further metabolized by conjugation with glucuronic acid. The glucuronide metabolites of morphine are morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Morphine and M6G are known to have analgesic activity in humans. The analgesic activity of C6G in humans is unknown. Norcodeine and M3G are generally not considered to possess analgesic properties.
Elimination: Approximately 90% of the total dose of Codeine (Comfarol) is excreted through the kidneys, of which approximately 10% is unchanged Codeine (Comfarol). Plasma half-lives of Codeine (Comfarol) and its metabolites have been reported to be approximately 3 hours.
Actions of Paracetamol (Comfarol) in details
Pharmacology: Paracetamol (Comfarol) exhibits analgesic and antipyretic activity by inhibiting prostaglandin synthesis. It produces analgesia by elevating the pain threshold and antipyresis through action on the hypothalamic heat-regulating center.
In therapeutic doses, Paracetamol (Comfarol)'s analgesic and antipyretic action is comparable to that of aspirin. Paracetamol (Comfarol) does not adversely affect platelet function and hemostasis.
Pharmacokinetics: Paracetamol (Comfarol) is rapidly and completely absorbed after oral administration. Peak plasma concentrations occur between 15 min to 2 hrs after ingestion. The absolute oral bioavailability of Paracetamol (Comfarol) is about 80% and is independent of dose in the range of 5-20 mg/kg.
Paracetamol (Comfarol) is not bound to plasma proteins to any extent. The concentrations of Paracetamol (Comfarol) in saliva are similar to those in plasma. Concentrations in whole blood are up to 20% higher and in breast milk about 20% lower than the plasma concentration. Paracetamol (Comfarol) crosses the placenta.
Paracetamol (Comfarol) is extensively metabolized in the liver and the total body clearance is about 5 mL/kg/min. The clearance of Paracetamol (Comfarol) is reduced and the half-life increased following a hepatotoxic overdose. Prolongation of half-life beyond 4 hrs usually indicates impending liver damage.
Two to five percent of a therapeutic dose of Paracetamol (Comfarol) is excreted unchanged in the urine. Its renal clearance is about 10 mL/min and is weakly dependent on urine flow rate but not on pH.
Paracetamol (Comfarol) administration
May be taken with or without food.
Paracetamol (Comfarol) pharmacology
The analgesic, antipyretic, and anti-inflammatory effects of aspirin are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Paracetamol (Comfarol) directly and irreversibly inhibits the activity of both types of cyclo-oxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes aspirin different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Paracetamol (Comfarol)'s antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation–inhibiting effect of aspirin specifically involves the compound's ability to act as an acetyl donor to the platelet membrane; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Paracetamol (Comfarol) affects platelet function by inhibiting the enzyme prostaglandin cyclooxygenase in platelets, thereby preventing the formation of the aggregating agent thromboxane A2. This action is irreversible; the effects persist for the life of the platelets exposed. Paracetamol (Comfarol) may also inhibit formation of the platelet aggregation inhibitor prostacyclin (prostaglandin I2) in blood vessels; however, this action is reversible.
References
- DailyMed. "CODEINE SULFATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Codeine Phosphate: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Codeine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Comfarol 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 Comfarol. 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
