Robitussin AC

Robitussin AC Uses, Dosage, Side Effects, Food Interaction and all others data.

The relief of pain (analgesia) is a primary goal for enhancing the quality of life of patients and for increasing the ability of patients to engage in day to day activities. Codeine, an opioid analgesic, was originally approved in the US in 1950 and is a drug used to decrease pain by increasing the threshold for pain without impairing consciousness or altering other sensory functions. Opiates such as codeine are derived from the poppy plant, Papaver somniferum (Papaveraceae).

Codeine is utilized as a central analgesic, sedative, hypnotic, antinociceptive, and antiperistaltic agent, and is also recommended in certain diseases with incessant coughing.

General effects

Guaifenesin possesses a storied history, having been originally formally approved by the US FDA in 1952 and continues to be one of very few - if not perhaps the only drug that is readily available and used as an expectorant . Since that time the agent has been a combination component of various prescription and non-prescription over-the-counter cough and cold products and is currently a widely available over-the-counter generic medication . Although it is principally believed that guaifenesin elicits an action to facilitate productive cough to manage chest congestion , it is not known whether the agent can reliably mitigate coughing.

Regardless, on March 1, 2007, the FDA received a petition asking the FDA to notify the public that some antitussives, expectorants, decongestants, antihistamines, and cough/cold combinations are not known to be safe and effective in children under the age of 6 years . After the negotiation between FDA and major manufacturers, a voluntary transition of labels for not using guaifenesin in children under the age of 4 years was endorsed by FDA in 2008 .

Furthermore, there has also been contemporary research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist .

Pheniramine is an alkylamine derivative with histamine H1-receptor antagonist effects. It also has anticholinergic and moderate sedative effects.

Pheniramine acts as an antagonist to allergic symptoms stemming from inappropriate histamine release to reduce edema, itching, and redness. The same antihistamine effect also produces sedation by acting in the central nervous system.

Trade Name Robitussin AC
Generic codeine + pheniramine + guaifenesin
Type
Therapeutic Class
Manufacturer
Available Country Canada, United States,
Last Updated: September 19, 2023 at 7:00 am
Robitussin AC
Robitussin AC

Uses

Codeine is an opioid analgesic used to treat moderate to severe pain when the use of an opioid is indicated.

Codeine sulfate is a form of this drug that is commonly used. It is available in tablet form and indicated for the relief of mild to moderately severe pain, where the use of an opioid analgesic is appropriate .

The solution form is used by itself or combined in a syrup with other drugs and is used as a cough suppressant in adults aged 18 and above , .

Guaifenesin is an expectorant commonly found in OTC products for the symptomatic relief from congested chests and coughs associated with cold, bronchitis, and/or other breathing illnesses.

Guaifenesin is an expectorant that is indicated for providing temporary symptomatic relief from congested chests and coughs which may be due to a cold, bronchitis, and/or other breathing illnesses .

Pheniramine is a competitive H1 histamine receptor antagonist. Like other alkylamine antihistamines it is also antagonist of muscarinic cholinergic receptors and possesses local anesthetic properties. However, the concentration required for the latter effect is probably not achieved at therapeutic dose

Pheniramine Maleate is used for allergic conditions (hypersensitivity reactions) such as:

  • Hay fever (pollinosis) with attacks of sneezing, itching, running of the nose, conjunctivitis.
  • Urticaria with pruritus and reddening, wealing and swelling of the skin.
  • Eczema of nervous origin (neurodermatitis) with pruritus.

Robitussin AC is also used to associated treatment for these conditions: Common Cold, Cough, Flu caused by Influenza, Mild pain, Pain, Severe Pain, Dry cough, Moderate Pain, Upper respiratory symptoms, Airway secretion clearance therapyAllergic Reaction, Asthma, Asthma, Allergic, Bronchial Asthma, Bronchitis, Bronchospasm, Chronic Bronchitis, Chronic Obstructive Respiratory Diseases, Common Cold, Cough, Cough caused by Common Cold, Coughing caused by Allergies, Coughing caused by Flu caused by Influenza, Drug Allergy, Emphysema, Fever, Flu caused by Influenza, Food Allergy, Headache, House dust allergy, Irritative cough, Laryngitis, Nasal Congestion, Nasal Congestion caused by Common Cold, Phlegm, Pollen Allergy, Productive cough, Rash, Rhinorrhoea, Sneezing, Sore Throat, Tracheitis, Urticaria, Whooping Cough, Acute Rhinitis, Chest congestion, Chills occurring with fever, Dry cough, Excess mucus or phlegm, Mild to moderate pain, Minor aches and pains, Airway secretion clearance therapy, ExpectorantAllergic Skin Reaction, Allergic urticaria, Anaphylaxis, Angioedema, Burns first degree, Common Cold, Congestion of the Conjunctivas, Dermatitis, Eczematous, Drug hypersensitivity reaction, Flu caused by Influenza, Insect Bites, Neurodermatitis, Ocular Irritation, Red eye, Seasonal Allergic Conjunctivitis, Sunburn, Urticaria

How Robitussin AC works

Codeine is a selective agonist for the mu opioid receptor, but with a much weaker affinity to this receptor than morphine, a more potent opioid drug. Codeine binds to mu-opioid receptors, which are involved in the transmission of pain throughout the body and central nervous system , . The analgesic properties of codeine are thought to arise from its conversion to Morphine, although the exact mechanism of analgesic action is unknown at this time , .

Although the exact mechanism of action of guaifenesin may not yet be formally or totally elucidated, it is believed that expectorants like guaifenesin function by increasing mucus secretion . Moreover, it is also further proposed that such expectorants may also act as an irritant to gastric vagal receptors, and recruit efferent parasympathetic reflexes that can elicit glandular exocytosis that is comprised of a less viscous mucus mixture . Subsequently, these actions may provoke coughing that can ultimately flush difficult to access, congealed mucopurulent material from obstructed small airways to facilitate a temporary improvement for the individual .

Consequently, while it is generally proposed that guaifenesin functions as an expectorant by helping to loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive, there has also been research to suggest that guaifenesin possesses and is capable of demonstrating anticonvulsant and muscle relaxant effects to some degree possibly by acting as an NMDA receptor antagonist .

Pheniramine competes with histamine for the histamine H1 receptor, acting as an inverse agonist once bound. The reduction in H1 receptor activity is responsible for reduced itching as well as reduced vasodilation and capillary leakage leading to less redness and edema. This can be seen in the suppression of the histamine-induced wheal (swelling) and flare (vasodilation) response. Inverse agonism of the H1 receptor in the CNS is also responsible for the sedation produced by first-generation antihistamines like pheniramine. The binding of pheniramine to H4 receptors, and subsequent inverse agonism, may also contribute to reduced itching by antagonizing inflammation.

Dosage

Robitussin AC dosage

Unless otherwise prescribed by the doctor, the following dosages are recommended for the different dosage forms:

Pheniramine Maleate Injection Solution: Except in life threatening conditions, the initial dose should be kept as low as possible: particularly in small children, a daily dose of 3 mg active substance per kg body weight should not be exceeded.

The following doses are administered once or twice daily:

  • Adults and Young people aged 12 years or over:1.0-2.0 ml IV/IM.
  • Children aged 1-2 years (about 11-14 kg body weight):0.5-0.7 ml IM only
  • Children aged 3-5 years (about 20 kg body weight):0.8-1.3 ml IM only
  • Children aged 6-11 years (upto about 25 kg body weight):1.0-1.5 ml IM only

Pheniramine Maleate Injection (45.5 mg/2 ml)

: This is administered to adults and young people aged 12 years or over either slowly by intravenous route (1 ml per minute) or intramuscularly. To infants and children up to 12 years old the injection must only be given intramuscularly. The recommended dose may be repeated at 12 hourly intervals until acute symptoms have subsided. Pheniramine Maleate can be combined with commercial calcium preparations but the compatibility should be tested in individual case.

Pheniramine Maleate Tablet (22.7 mg): In adults and young people of over 12 years of age it is advisable to begin treatment with 1 tablet 2-3 times daily after meals. If necessary, the daily dose may be increased to 2 tablets 3 times daily from the second day of treatment onwards.

Pheniramine Maleate Syrup (15 mg/5 ml): is particularly suitable for children. Children aged 1-3 years should receive half a measuring spoonful two or three times daily; children aged 4-12 years, 1 measuring spoonful 2 or 3 times daily; adults and young people 1-2 measuring spoonful of syrup twice or three times a day after meals. A daily dose of 3 mg/kg body weight must not be exceeded. Diabetics must bear in mind that Pheniramine Maleate Syrup contains carbohydrates which are equivalent to 1.75 gm glucose per measuring spoonful (5 ml)

Pheniramine Maleate RetardTablet (75 mg): The coated tablets have a prolonged action. In most adults and adolescent over 12 years of age 1 coated tablet taken after supper is sufficient to produce an antihistaminic effect that for up to 24 hours. Only in very resistant cases will it be necessary to give an additional coated tablet in the morning after breakfast. The tablets are swallowed whole with a little liquid.

Side Effects

Occasionally there may be drowsiness, gastrointestinal complaints, dryness of mouth, palpitation, urinary retention or hypersensitivity reactions. In isolated cases, higher doses may produce hallucinations, restlessness or confusion; in small children, agitation.

In patients with narrow angle-glaucoma a rise in intraocular pressure is possible, which makes opthalmologic control necessary.

Even if used according to prescription, these preparations may reduce alertness to such an extent that the ability to cope with street traffic or operate machinery is impaired.

Toxicity

Oral LD50: 427 mg kg-1 (rat) .

Overdose/toxicity

Symptoms of opioid toxicity may include confusion, somnolence, shallow breathing, constricted pupils, nausea, vomiting, constipation and a lack of appetite. In severe cases, symptoms of circulatory and respiratory depression may ensue, which may be life-threatening or fatal , .

Teratogenic effects

This drug is classified as a pregnancy Category C drug. There are no adequate and well-controlled studies completed in pregnant women. Codeine should only be used during pregnancy if the potential benefit outweighs the potential risk of the drug to the fetus .

Codeine has shown embryolethal and fetotoxic effects in the hamster, rat as well as mouse models at about 2-4 times the maximum recommended human dose . Maternally toxic doses that were about 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of bone resorption and incomplete bone ossification. Codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison .

Nonteratogenic effects

Neonatal codeine withdrawal has been observed in infants born to addicted and non-addicted mothers who ingested codeine-containing medications in the days before delivery. Common symptoms of narcotic withdrawal include irritability, excessive crying, tremors, hyperreflexia, seizures, fever, vomiting, diarrhea, and poor feeding. These signs may be observed shortly following birth and may require specific treatment .

Codeine (30 mg/kg) given subcutaneously to pregnant rats during gestation and for 25 days after delivery increased the rate of neonatal mortality at birth. The dose given was 0.8 times the maximum recommended human dose of 360 mg/day .

The use in breastfeeding/nursing

Codeine is secreted into human milk. The maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants .

The most prevalent signs and symptoms associated with an overdose of guaifenesin have been nausea and vomiting .

Although adequate and well-controlled studies in pregnant women have not been performed, the Collaborative Perinatal Project monitored 197 mother-child pairs exposed to guaifenesin during the first trimester . An increased occurrence of inguinal hernias was found in the neonates . However, congenital defects were not strongly associated with guaifenesin use during pregnancy in 2 large groups of mother-child pairs .

Moreover, guaifenesin is excreted in breast milk in small quantities . Subsequently, caution should be exercised by balancing the potential benefit of treatment against any possible risks .

Additionally, an LD50 value of 1510 mg/kg (rat, oral) has been reported for guaifenesin .

Case reports involving pheniramine overdosage mention the rare possibility of arrythmias, cutaneous eruptions, and rhabdomyolysis with acute kidney injury. The administration of activated charcoal effectively prevents the absorption of pheniramine as it largely adsorbs to the charcoal, therefore this may be of benefit in cases of overdose if provided early after ingestion.

Precaution

During pregnancy and lactation, pheniramine should be used only if strictly indicated, and after considering the benifit/risk ratio for mother and child.

Interaction

The effect of drugs which act on the central nervous system (e.g. tranquilizers, sedatives, neuroleptic agents and MAO inhibitors) and of alcohol may be potentiated.

Volume of Distribution

Apparent volume of distribution: about 3-6 L/kg, showing an extensive distribution of the drug into tissues .

The geometric mean apparent volume of distribution of guaifenesin determined in healthy adult subjects is 116L (CV=45.7%) .

Elimination Route

Absorption

Codeine is absorbed from the gastrointestinal tract. The maximum plasma concentration occurs 60 minutes after administration .

Food Effects

When 60 mg codeine sulfate was given 30 minutes post-ingestion of a high high-calorie meal, there was no significant change in the absorption of codeine .

Steady-state concentration

The administration of 15 mg codeine sulfate every 4 hours for 5 days lead to steady-state concentrations of codeine, morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) within 48 hours .

Studies have shown that guaifenesin is well absorbed from and along the gastrointestinal tract after oral administration .

The administration of 30.5 mg of free base pheniramine resulted in a Cmax of 173-294 ng/L with a Tmax of 1-2.5 h.

Half Life

Plasma half-lives of codeine and its metabolites have been reported to be approximately 3 hours .

The half-life in plasma observed for guaifenesin is approximately one hour .

The terminal half-life of pheniramine administered via IV is 8-17 h.

Clearance

Renal clearance of codeine was 183 +/- 59 ml min-1 in a clinical study .

Renal impairment may decrease codeine clearance .

The mean clearance recorded for guaifenesin is about 94.8 L/hr (CV=51.4%) .

Elimination Route

About 90% of the total dose of codeine is excreted by the kidneys. Approximately 10% of the drug excreted by the kidneys is unchanged codeine .

The majority of the excretion products can be found in the urine within 6 hours of ingestion, and 40-60 % of the codeine is excreted free or conjugated, approximately 5 to 15 percent as free and conjugated morphine, and approximately 10-20% free and conjugated norcodeine .

After administration, guaifenesin is metabolized and then largely excreted in the urine .

Pheniramine is eliminated by metabolism and via renal excretion. 24.3% of pheniramine is present in the urine as the parent drug.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Hypersensitivity to pheniramine. The Syrup is contraindicated in patients hypersensitive to Methyl Hydroxybenzoate and Propyl Hydroxybenzoate. Prostatic hypertrophy with residual urine formation.

Acute Overdose

Symptoms: Agitation and convulsions (especially in children), and restlessness, disorientation and hallucinations in adults. Accidental ingestion in small children has resulted in convulsions and in some cases fatal.

Treatment: No specific antidote; symptomatic and supportive. Gastric lavage may be useful for some time after ingestion. Do not use stimulants. Diazepam or short-acting barbiturates may be used to control convulsions. Vasopressors may be used for hypotension.

Storage Condition

Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician. Do not use later than the date of expiry.

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