Description and composition of Zedex D Capsule
Zedex D Capsule is a medicine used for the treatment of cold and flu. It contains Acetaminophen 325mg, Dextromethorphan Hydrobromide 10 and Doxylamine Succinate 25mg, as its active ingredients. It also contains other inactive ingredients called excipients in sufficient quantities.
ZEDEX D is a fixed dose combination of acetaminophen, dextromethorphan hydrobromide and Doxylamine Succinate
Clinical Pharmacology
Pharmacodynamics
Acetaminophen is a centrally acting analgesic and antipyretic with minimal anti-inflammatory properties. The mechanisms of action of acetaminophen in reducing pain is unknown but may be due to inhibition of central prostaglandins synthesis and elevation of pain threshold.
Acetaminophen reduces fever by inhibiting the formulation and release of prostaglandin in the CNS and by inhibiting endogenous pyrogens at the hypothalamic thermoregulator center.
Dextromethorphan is a non-opioid cough suppressant. It is the methylated dextrorotatory analogue of levorphanol, a codeine analogue.
Dextromethorphan acts centrally on the cough centre the medulla and nucleus tractus Solaris to increase the cough threshold.
It does not have classical analgesic, sedative or respiratory depressant effects at usual antitussive doses.
Doxylamine succinate competes with histamine at central and peripheral histamine 1receptor sites, preventing the histamine receptor interaction and subsequent mediator release.
This may alleviate the symptoms of runny nose and sneezing
Pharmacokinetics
Paracetamol
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake delays paracetamol absorption.
Paracetamol is distributed into most body tissues. Binding to the plasma proteins is minimal at therapeutic concentrations but increases with increasing doses.
Paracetamol is metabolised extensively in the liver, mainly to N-acetyl-p-benzoquinone imine. It is excreted in the urine majorly as inactive glucuronide and sulphate conjugates.
The elimination half-life is 2-3 hours in adults.
Dextromethorphan
After oral administration, dextromethorphan is quickly absorbed in the gastrointestinal tract with peak serum levels reached within 2-2.5 hours.
Dextromethorphan is absorbed from the bloodstream and crosses the blood-brain into the cerebral spinal fluid by approximately 33-80%.
The antitussive activity of dextromethorphan lasts for approximately 5-6 hours with plasma half live of 2-4 hours.
Dextromethorphan is rapidly metabolized by the liver and is O-demethylated to produce its active mataboite dextrorphan.
Dextromethorphan is then further N-demethylated and partially conjugated with glucuronic acid and sulfate ions.
Cytochrome P450 in the 2D6 isoenzyme family inactivates dextromethorphan
Doxylamine succinate
Doxylamine succinate is readily absorbed from the gastrointestinal tract. Following oral administration, the mean peak plasma concentration occurs after 2-3 hours.
It has an elimination half life of about 10 hours in healthy adults. It is excreted in the urine as unchanged doxylamine (60%) and metabolites (nordoxylamine and dinordoxylamino).
The major metabolic site is the liver and major metabolic pathways are N-demethylation, N-oxidation, hydroxylation, N-acetylation, N-desalkylation and ether cleavage
Indications and uses of Zedex D Capsule
Zedex D Capsule is used for temporary relief in common cold and flu symptoms like minor aches and pains, headache, sore throat, fever, Sneezing, nose and cough due to minor throat and bronchial imitation.
Dosage and Administration
Adults and children above 12 years: One to two capsules to be administered every 4-6 hours. Do not exceed 8 capsules in 24 hours
Contraindications
Zedex D is contraindicated in patients showing hypersensitivity to any of the components of the product.
Acetaminophen containing product is contraindicated in active and severe hepatic disease and severe hepatic impairment.
This product is also contraindicated in patients who are tasking monoamine oxidase inhibitors (MAOIs), or who have taken MAOIs within the previous 14 days, with, or at risk of developing respiratory failure, with narrow angle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction and pyloroduodenal obstruction
Warnings and Precautions
Skin reactions, serious and potentially fatal (e.g, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis) have been reported with acetaminophen.
Discontinue use at first appearance of rash or other sign of hypersensitivity.
Use with caution in patients taking beta-blockers and other antihypertensive drugs, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI) and monoamine oxidase inhibitors (MAOI).
Doxylamine succinate should be used with caution in patients with renal or hepatic impairment and epilepsy. The elderly may experience paradoxical excitation with doxylamine succinate. They are more likely to have central nervous system (CNS) depressive side effects, including confusion.
Concomitant use of alcohol and other cough and cold medicines should be avoided.
Do not take offer Acetaminophen containing medicines.
Do not exceed recommended dosage.
Patients should be advised not to drive or operate machinery if affected by drowsiness or dizziness
Use in pregnancy
Category B2. This product should be prescribed in pregnancy only if benefits outweigh risks.
Use in lactation
Caution should be undertaken while prescribing this product to lactating women. Paracetamol is excreted in breast milk. Maternal ingestion of paracetamol in usual analgesic doses does not appear to present a risk to the breastfed infants.
Phenylephrine may be excreted in breast milk. It is not known whether dextromethorphan is excreted in breast milk or whether it has harmful effect on the breastfeeding infant.
Use in Children
Do not give to children under 12 years of age.
Drug Interactions
Anticoagulant dosage may require reduction if treatment with paracetamol-containing medication is prolonged.
Substances that increase gastric emptying (e.g. metoclopramide) increase paracetamol absorption.
Substances that decrease gastric emptying (e.g. propantheline, antidepressants with anticholinergic properties, narcotic analgesics) decrease paracetamol absorption.
Chloramphenicol concentrations may be increased by paracetamol.
Potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes (e.g alcohol, anticonvulsants) may increase risk of paracetamol toxicity.
Probenecid may affect paracetamol excretion and alter paracetamol plasma concentrations.
Colestyramine reduces the absorption of paracetamol if given within one hour of paracetamol.
Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIS within the previous 14 days.
Concomitant use of dextromethorphan with selective serotonin re-uptake inhibitors (SSRIs) such as fluoxetine or tricyclic antidepressants such as clomiprmine and imipramine, may result in serotonin syndrome. Concomitant use of dextromethorphan and other CNS depressants (e.g. alcohol, narcotic analgesics and tranquillizers) may increase the CNS depressant effects of these drugs. Serum levels of dextromethorphan may be increased by the concomitant use of inhibitors of cytochrome P450 206.
Central nervous system (CNS) depressants (alcohol, sedatives, opioid analgesics, hypnotics) may cause an increase in sedation effects of doxylamine succinate.
Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) may prolong and intensify the anticholinergic and CNS depressive effects of doxylamine.
Side effects of Zedex D Capsule
Adverse reactions reported to occur very rarely due to paracetamol ingestion are:
- Thrombocytopenia, anaphylaxis; cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome; bronchospasm; and hepatic dysfunction
Uncommon adverse effects reported with dextromethorphan administration are:
- Drowsiness, dizziness, fatigue, dystonia, gastrointestinal disturbance, nausea, vomiting, abdominal discomfort or constipation.
Very rarely allergic reactions and serotonin syndrome when concurrently taken with MAOIs or serotonergic drugs may occur.
Doxylamine succinate may cause CNS depressive effects including sedation and impaired performance.
CNS stimulatory effects of doxylamine succinate may include anxiety, hallucinations, appetite stimulation, muscle dyskinesias and activation of epileptogenic foci.
High doses of doxylamine succinate may cause nervousness, tremor, insomnia, agitation, and irritability.
Anticholinergic effects of doxylamine succinate associated with cholinergic blockage include dryness of the eyes, mouth and nose, blurred vision, urinary hesitancy and retention, constipation and tachycardia.
What to do in Overdosage of Zedex D Capsule
Stop administration of product immediately. Most mild to moderate toxicity cases will need symptomatic and supportive care.
Give activated charcoal if patient presents shortly after ingestion; sedate with benzodiazepines for agitation and delirium.
Hypertension and tachycardia are generally mild and well tolerated, and do not require specific treatment.
Physostigmine can be used to establish a diagnosis. Severe cases of paracetamol intoxication should be initiated with N-Acetylcysteine (NAC) as the antidote.
How to store Zedex D Capsule
Store below 30°C. Protect from light and moisture. Keep out of reach of children.
Presentation
ZEDEX D is available as 10 capsules in a blister.