| Active ingredients | Chemical structure | CAS Registry Number |
| Paracetamol | 103-90-2 | |
| Phenylephrine Hydrochloride | 61-76-7 | |
| Dextromethorphan Hydrobromide | 6700-34-1 |
Blue capsule-shaped tablets (caplets) with flat edges, one face is embossed with a within an oval.
Active Ingredients per caplet:
Paracetamol 500 mg Phenylephrine Hydrochloride 5 mg Dextromethorphan Hydrobromide 15mg
Excipients:
Cellulose - microcrystalline Indigo carmine Potassium sorbate Povidone Sodium lauryl sulfate Starch - maize Starch - pregelatinised maize Stearic acid Talc - purified
Pharmacodynamics
Paracetamol is a para-aminophenol derivative that exhibits analgesic and anti-pyretic activity. It does not possess anti-inflammatory activity. Paracetamol is thought to produce analgesia through a central inhibition of prostaglandin synthesis. Phenylephrine acts predominantly by a direct effect on alpha adrenergic receptors. Phenylephrine also has an indirect effect by releasing noradrenaline from its storage sites. Phenylephrine is used as a nasal decongestant to provide symptomatic relief by causing vasoconstriction resulting in redistribution of local blood flow to reduce oedema of the nasal mucosa, thus improving ventilation, drainage and nasal stuffiness. 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 in 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.
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 and excreted in the urine mainly as inactive glucuronide and sulphate conjugates. The metabolites of paracetamol include a minor hydroxylated intermediate which has hepatotoxic activity. This intermediate metabolite is detoxified by conjugation with glutathione. However, it can accumulate following paracetamol overdosage (more than 150 mg/kg or 10 g total paracetamol ingested) and, if left untreated, can cause irreversible liver damage. Paracetamol is metabolised differently by premature infants, newborns, infants and young children compared to adults, the sulfate conjugate being predominant. Paracetamol is excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted unchanged. Approximately 85% of a dose of paracetamol is excreted in urine as free and conjugated paracetamol within 24 hours of ingestion. The elimination half- life varies from one to three hours. Administration of paracetamol to patients with moderate to severe renal impairment may result in accumulation of paracetamol conjugates
Dextromethorphan Hydrobromide
Dextromethorphan
is well absorbed from the gastrointestinal tract after oral administration.
Dextromethorphan is metabolised in the liver, exhibiting polymorphic metabolism involving the cytochrome P450 isoenzyme (CYP 2D6).. Dextromethorphan is excreted in the urine as unchanged dextromethorphan and demethylated metabolites, including dextrorphan, which has some cough suppressant activity. The plasma elimination half-life of dextromethorphan is 1.2 to 3.9 hours. However, the rate of metabolism varies between individuals according to phenotype (extensive v poor metabolisers), with half- life being as long as 45 hours in patients who are poor metabolisers.
Phenylephrine Hydrochloride
Phenylephrine
is irregularly absorbed from the gastrointestinal tract. Phenylephrine undergoes first-pass metabolism by monoamine oxidases in the gut and liver; orally administered phenylephrine thus has reduced bioavailability.
Phenylephrine undergoes extensive metabolism in the intestinal wall (first pass) and in the liver. The principal routes of metabolism involve sulfate conjugation (primarily in the intestinal wall) and oxidative deamination (by monoamine oxidase); glucuronidation also occurs to a lesser extent. Phenylephrine undergoes rapid distribution into peripheral tissues. The volume of distribution of phenylephrine is between 200 and 500L, there appears to be minimal brain penetration, and does not seem to cross the placenta and does not appear to be distributed to any great extent in breast milk. Phenylephrine and its metabolites are excreted mainly in urine. Following oral administration approximately 80% of the dose is excreted in urine within 48 hours principally as metabolites. Approximately 2.5% of an oral dose is excreted in the urine as unchanged drug. The elimination half life averages 2-3 hours following oral administration.
For the temporary relief of the following symptoms of colds and flu: headache, runny or blocked nose, sore throat, dry cough, body aches and pains. Reduces fever.
This product is contraindicated in patients: with a previous history of hypersensitivity to paracetamol, phenylephrine hydrochloride, dextromethorphan hydrobromide or any of the excipients. who are taking monoamine oxidase inhibitors (MAOIs), or who have taken MAOIs within the previous 14 days,. (See INTERACTIONS.) with severe hypertension or coronary artery disease who are taking other sympathomimetics (such as decongestants, appetite suppressants and amphetamine-like psychostimulants). (See INTERACTIONS) with, or at risk of developing respiratory failure (e.g. those with chronic obstructive airways disease or pneumonia or during an asthma attack or an exacerbation of asthma). Who are using other medicines containing paracetamol, phenylephrine, dextromethorphan or other medicines for the relief of coughs & colds, congestion or blocked nose. Concomitant use of other cough and cold medicines should be avoided.
Medical advice should be sought before taking this product in patients with these conditions: Chronic or persistent cough such as occurs with asthma and emphysema or where cough is accompanied by excessive secretions. Bronchitis Bronchiectasis Bronchial asthma Hypertension Cardiovascular disease Diabetes Hyperthyroidism Glaucoma Phaeochromocytoma An enlargement of the prostate gland Occlusive vascular disease (e.g. Raynaud's Phenomenon) Liver and kidney impairment. Underlying liver disease increases the risk of paracetamol-related liver damage. Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication. Use with caution in patients taking the following medication: Beta-blockers and other antihypertensive drugs Tricyclic antidepressants Selective serotonin reuptake inhibitors (SSRI) (See INTERACTIONS.) Concomitant use of alcohol should be avoided (See INTERACTIONS). Medical advice should be sought if the cough persists or is accompanied by high fever, skin rash or persistent headache. Keep out of sight and reach of children.
This product should not be used during pregnancy without medical advice.
Category B2
Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of foetal damage.
This product should not be used whilst breast feeding without medical advice. 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.
Do not give to children under 12 years of age. Effects on ability to drive and use machinery Patients should be advised not to drive or operate machinery if affected by drowsiness or dizziness.
The following interactions with paracetamol have been noted:
| Coumarins (including warfarin) | Anticoagulant effect may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding. Anticoagulant dosage may require reduction if treatment with paracetamol-containing medication is prolonged. |
| Substances that increase gastric emptying (e.g. metoclopramide) | These substances increase paracetamol absorption. |
| Substances that decrease gastric emptying (e.g. propantheline, antidepressants with anticholinergic properties, narcotic analgesics) | These substances decrease paracetamol absorption. |
| Chloramphenicol | Concentrations may be increased by paracetamol |
| Potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes (e.g. alcohol, anticonvulsants) | Risk of paracetamol toxicity may be increased. |
| Probenecid | May affect paracetamol excretion and alter paracetamol plasma concentrations. |
| Colestyramine | Reduces the absorption of paracetamol if given within one hour of paracetamol. |
Phenylephrine should be used with caution in combination with the following drugs as interactions have been reported.
| Monoamine oxidase inhibitors | Hypertensive crisis or a serious increase in blood pressure may occur between phenylephrine and monoamine oxidase inhibitors (See CONTRAINDICATIONS.) |
| Sympathomimetic amines such as other decongestants, appetite suppressants and amphetamine- | Concomitant use of phenylephrine with other sympathomimetic amines can increase the risk of cardiovascular side effects and other additive effects (See |
| like psychostimulants | PRECAUTIONS.) |
| Beta-blockers and other antihypertensives (including debrisoquine, guanethidine, reserpine, methyldopa) | Phenylephrine may reduce the efficacy of beta-blocking drugs and antihypertensive drugs. The risk of hypertension and other cardiovascular side effects may be increased. (See PRECAUTIONS.) |
| Tricyclic antidepressants (e.g. amitriptyline) | May increase the risk of cardiovascular side effects with phenylephrine (See PRECAUTIONS.) Hypertensive crisis may also occur. |
| Digoxin and cardiac glycosides | Increase the risk of irregular heartbeat or heart attack. |
The following interactions with dextromethorphan have been noted:
| Monoamine oxidase inhibitors (MAOIs) | Dextromethorphan should not be used in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken MAOIs within the previous 14 days. The use of dextromethorphan with, or within two weeks of taking MAOIs, may increase the risk of serious side effects such as hypertensive crisis, hyperpyrexia and convulsions. |
| Selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants | 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 with changes in mental status, hypertension, restlessness myoclonus, hyperreflexia, diaphoresis, shivering and tremor. |
| CNS depressants (e.g. alcohol, narcotic analgesics and tranquilizers) | Concomitant use of dextromethorphan and other CNS depressants (e.g. alcohol, narcotic analgesics and tranquillizers) may increase the CNS depressant effects of these drugs. (See PRECAUTIONS.) |
| Inhibitors of cytochrome P450 2D6 | Serum levels of dextromethorphan may be increased by the concomitant use of inhibitors of cytochrome P450 2D6, such as the anti-arrhythmic quinidine and amiodarone, antidepressants such as fluoxetine and paroxetine, or other drugs which inhibit cytochrome P450 2D6 such as haloperidol and thioridazine. |
Adverse events from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled doses and considered attributable are tabulated below by System Organ Class and frequency. The following convention has been utilised for the classification of undesirable effects: very common (>=1/10), common (>=1/100, <1/10), uncommon (>=1/1,000, <1/100), rare (>=1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated from available data). Adverse event frequencies have been estimated from spontaneous reports received through post-marketing data.
Paracetamol
The frequency of these reactions is unknown but considered likely to be very rare.
| Body System | Undesirable Effect |
| Blood and lymphatic system disorders | Thrombocytopenia |
| Immune system disorders | Anaphylaxis Cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm |
| Hepatobiliary disorders | Hepatic dysfunction |
Phenylephrine
The following adverse events have been observed in clinical trials with phenylephrine and may therefore represent the most commonly occurring adverse events
| Body System | Undesirable Effect |
| Psychiatric disorders | Nervousness |
| Nervous system disorders | Headache, dizziness, insomnia |
| Cardiac disorders | Increased blood pressure |
| Gastrointestinal disorders | Nausea, vomiting |
| Central nervous stimulation | Anxiety |
Adverse reactions identified during post-marketing use are listed below.
| Body System | Undesirable Effect | Frequency |
| Eye disorders | Mydriasis, acute angle closure glaucoma, most likely to occur in those with closed angle glaucoma (See PRECAUTIONS.) | Rare |
| Cardiac disorders | Tachycardia, palpitations | Rare |
| Skin and subcutaneous disorders | Allergic reactions (e.g. rash, urticaria, allergic dermatitis) | Rare |
| Renal and urinary disorders | Dysuria, urinary retention. This is most likely to occur in those with bladder outlet obstruction such as prostatic hypertrophy. | Rare |
Dextromethorphan
The following adverse events have been observed in clinical trials and are likely to represent uncommon adverse reactions to dextromethorphan(i.e. occurring in >=1/1,000 to 141 <1/100 patients). Adverse reactions are listed below by MedDRA System Organ Class..
| Body System | Undesirable Effect |
| Nervous system disorders | Drowsiness, dizziness, fatigue, dystonia |
| Gastrointestinal disorders | Gastrointestinal disturbance, nausea, vomiting, abdominal discomfort or constipation |
Adverse reactions identified during post-marketing use are listed below. The frequency of these reactions is unknown but likely to be very rare (occurring in < 1/10,000 patients).
| Body System | Undesirable Effect | Frequency |
| Immune system disorder , skin and subcutaneous disorders | Allergic reactions (e.g. rash, urticaria, allergic dermatitis) | Very rare |
| Nervous system disorders | Serotonin syndrome (with changes in mental status, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering, tremor and hypertension) has been reported when dextromethorphan has been taken concurrently with MAOIs or serotonergic drugs such as SSRIs (see CONTRAINDICATIONS, PRECAUTIONS and INTERACTIONS). | Very rare |
Adults and children aged 12 years and over:
2 caplets every 4 - 6 hours as necessary. Maximum 8 caplets in 24 hours.
Do not use for more than a few days at a time in adults except on medical advice. Should not be used for more than 48 hours for children aged 12 - 17 except on medical advice. Do not give to children under 12 years of age. Do not exceed the stated dose. Should not be used with other medicines containing paracetamol, dextromethorphan, phenylephrine or decongestants including other cough and cold medicines. Do not use within several hours of going to bed as it may cause sleeplessness. Minimum dosing interval: 4 hours Renal and Hepatic impairment Patients who have been diagnosed with liver or kidney impairment must seek medical advice before taking this medication. The restrictions related to the use of such combinations in these patients is primarily a consequence of the paracetamol content of the product. (See PRECAUTIONS.)
Immediate medical management is required in the event of an overdose even if the symptoms of overdose are not present. If an overdose is taken or suspected, contact the Poisons Information Centre immediately for advice (13 11 26) or the patient should go to the nearest hospital straight away. This should be done even if they feel well because of the risk of delayed, serious liver damage.
Blue capsule-shaped tablets (caplets) with flat edges, one face is embossed with a sun graphic within an oval Blister packs of 24 caplets Store below 30oC
GlaxoSmithKline Consumer Healthcare 82 Hughes Avenue, Ermington, NSW 2115
S2 - Pharmacy Medicine
AUST R 148713 20 December 2007
April 2013 PANADOL(r) is a registered trade mark of the GlaxoSmithKline group of companies.