Pholcodine

Pholcodine is an analeptic agent (a stimulant of the central nervous system).

It is also used as cough suppressant for the temporary relief of non-productive dry cough.

Pholcodine is Readily absorbed from the gastrointestinal tract. Time to peak plasma concentration: 4-8 hour and enters breast milk. Volume of distribution: 30-49 L/kg. Plasma protein binding: 24% and get metabolised in the liver via hydrolysis followed by conjugation and N-dealkylation.The Elimination half-life was about 32-43 hours.

Pholcodine shows common side effects like Dysrrhythmias, seizure, HTN or hypotension, dyspnoea. Nervous: Confusion, convulsions, dizziness, hallucinations, headache, hyperactivity.

Pholcodine is available in the form of Solutions .

Pholcodine is available in India, Germany, Canada, Italy.

Pholcodine is a centrally acting cough suppressant that causes depression of the cough reflex, partly due to its direct effect on the cough centre in the medulla. It has a mild sedative effect with little or no analgesic action.

Pholcodine is indicated For use as a temporary measure in hospitalized patients with acute respiratory insufficiency superimposed on chronic obstructive pulmonary disease.

Pholcodine is approved for use in the following clinical indications

Pholcodine is indicated as a cough suppressant for the temporary relief of non-productive dry cough. It is stated to present a required label indication of "temporary relief of dry cough." Cough is the respiratory movement that occurs after an irritation signal is transmitted to the central nervous system and further stimulates the medulla oblongata. This stimulation causes a motor output that is sent through motoneurons to the respiratory muscles. A non-productive cough is a type of cough characterized by the absence of sputum, and it has a large inspiration that will cause continuous coughing.

Oral

Acute non-productive cough

Adult: 5-10 mg 3 or 4 times daily. Alternatively, 10-15 mg 8-10 hourly. Dosage recommendations may vary among countries or individual products.

Pholcodine is available in various strengths as 0.4 mg/mL, 1 mg/mL, 2 mg/mL, 3 mg/mL, 4 mg/mL

Pholcodine is available in the form of solutions.

Dosage Adjustment in Kidney Patient

• There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosage Adjustment in Hepatic impairment Patient

• There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, use caution in severe impairment due to the potential for altered pharmacokinetics.

Dosage Adjustment for Pediatric Patients

• 6-12 years 4 mg tid. Max treatment duration: 5 days; >12 years Same as adult dose. Dosage recommendations may vary among countries or individual products. Refer to specific product guidelines.

Patient at risk of developing respiratory failure. Asthma attack, chronic bronchitis, COPD, bronchiolitis or bronchiectasis. Hepatic failure. Children <6 years. Concomitant use with or within 14 days of stopping MAOI therapy.

Common Adverse effects:

Sputum retention; adrenal insufficiency, infertility (long-term use).

Gastrointestinal disorders: Nausea, vomiting, constipation.

Less common Adverse effects:

Occasional drowsiness, dizziness; ataxia (large dose).

Psychiatric disorders: Excitation, confusion; restlessness (large dose).

Rare Adverse effects:

Excitation, confusion; restlessness (large dose).

Respiratory, thoracic and mediastinal disorders: Respiratory depression (large dose).

Skin and subcutaneous tissue disorders: Rash.

Additive pressor effect when concurrently used w/ MAOIs or sympathomimetics. May temporarily mask the residual effect when used w/ neuromuscular blocking agents. May cause increased CNS stimulation, agitation, muscle fasciculation and hyperactivity w/ concurrent use of aminophylline/theophylline. Cardiac arrhythmias may occur when given w/ anaesthetics that are known to sensitise the myocardium to catecholamines (e.g. enflurane, halothane, isoflurane), delay initiation of Pholcodine for at least 10 min after discontinuance of anaesthesia.

The common side effects of Pholcodine include the following constipation, drowsiness, excitation, ataxia and respiratory depression have been reported occasionally or after large doses.

Symptoms: Restlessness, excitement, ataxia, drowsiness, nausea, and respiratory depression.

Management: Symptomatic and supportive treatment. Gastric emptying may be done by aspiration and lavage. Naloxone may be given in cases of acute poisoning. Administration of activated charcoal (1 g/kg) may also be considered if ingestion is >4 mg/kg, provided the airway is protected and ingestion is recent (within 1 hour).

Pharmacodynamic

The therapeutic doses of pholcodine have been shown not to cause depression of respiration, CNS excitation or other side effects associated with narcotics. It is thought that the impact of pholcodine is selective on the cough center without affecting the respiratory center. Pholcodine is not euphorigenic, and thus, psychological dependence is unlikely.

Pharmacokinetics

• Absorption

After oral administration of 60 mg of pholcodine, the Tmax and Cmax are reported to be 1.3 hours and 26.3 ng/ml. In the same administration, the AUC in plasma and saliva are reported to be 1.67 and 6.61 mg h/l respectively. The absorption of pholcodine is reported to represent approximately 88% of the administered dose.

• Distribution

The reported volume of distribution depends on the pharmacokinetic model and it can be of 265L based on a one-compartment model to 3207L in a two-compartment model.

• Metabolism

The metabolism of pholcodine seems to be very slow and due to the elimination profile, it is thought that most of the administered dose undergoes metabolism. There is some evidence in preclinical trials that indicate that morphine is a minor metabolite of pholcodine and that it accounts for 1% of the administered dose.

• Elimination

After oral administration of pholcodine, the serum concentration peaks and declines in a mono-exponential manner. The percent of the dose excreted unchanged is of approximately 25-30%. Part of the administered dose is composed by metabolites that can be recovered in urine. From the administered dose, the fecal excretion corresponds to the 5% of the administered dose as unchanged pholcodine.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Pholcodine?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/