A film coated, blue caplet (capsule shaped tablet) "PANADOL" printed on one face "NIGHT" on the other. Each tablet contains 500 mg of paracetamol, 25 mg of diphenhydramine hydrochloride and the following excipient ingredients: Starch - maize, opadry blue, potassium sorbate, povidone, talc - purified, starch pregelatinised maize, stearic acid
Paracetamol is a para-aminophenol derivative that exhibits analgesic and anti pyretic activity. The mechanism of action is believed to include inhibition of prostaglandin synthesis. It possesses a weak anti-inflammatory activity. It provides relief from mild to moderate pain and fever. Diphenhydramine hydrochloride is an ethanolamine class antihistamine that acts predominantly as a competitive but reversible inhibitor of histamine at the H1 receptor sites. It has additional sedative anticholinergic (antimuscarinic) and local anaesthetic properties.
After oral administration, paracetamol is absorbed rapidly and completely from the gastrointestinal tract; peak plasma levels occur 10 to 60 minutes after administration. Paracetamol is uniformly distributed throughout most body fluids; the apparent volume of distribution is 1 to 1.2 L/kg. Paracetamol can cross the placenta and is excreted in breast milk. Plasma protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations. Paracetamol is metabolised by the hepatic microsomal enzyme system. In adults at therapeutic doses, paracetamol is mainly conjugated with glucuronide (45 to 55%) or sulfate (20 to 30%). A minor proportion (less than 20%) is metabolised to catechol derivatives and mercapturic acid compounds via oxidation. Paracetamol is metabolised differently by infants and children compared to adults, the sulfate conjugate being predominant. Paracetamol is excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol with 85 to 90% of the administered dose eliminated in the urine within 24 hours of ingestion. The elimination half-life varies from 1 to 3 hours. Food intake delays paracetamol absorption. Diphenhydramine is well absorbed from the gastrointestinal tract following oral administration. It is subject to high first pass metabolism. Peak plasma concentrations are achieved 1to 4 hours after administration and the effects are maintained for 4 to 6 hours. It is widely distributed throughout the body including the CNS and is highly plasma protein bound. Diphenhydramine is metabolised extensively by the liver and is excreted mainly as metabolites in the urine. Excretion is largely complete within 24 hours of administration. Pharmacokinetic studies have also been conducted on the combination of paracetamol and diphenhydramine. The bioavailability of paracetamol from the combination product was shown to be similar to the bioavailability of paracetamol from PANADOL tablets. The Cmax and AUC(o-tn) of the diphenhydramine component of the combination product were slightly higher than from diphenhydramine tablets. The differences were small but statistically significantly. It is possible that the higher levels of diphenhydramine noted for the combination tablets may reflect competition between paracetamol and diphenhydramine for oxidative enzymes. The Tmax values for paracetamol from the combination product were slightly higher than Tmax from PANADOL tablets but the difference was not considered statistically significant. This suggests that the presence of diphenhydramine impacts minimally on the rate of gastric emptying at the recommended dose.
For the temporary relief of pain when associated with sleeping difficulty; for example, headache, migraine, backache, arthritis, rheumatic and muscle pain, neuralgia, toothache or period pain.
Adults and children over 12 years:
take 2 tablets with water or other fluid only at bedtime. Maximum 2 caplets within 24 hours.
A subsequent requirement for analgesia throughout the night should be provided by paracetamol alone. Products containing paracetamol may be taken for daytime pain relief but at a reduced maximum dose of 6 tablets in 24 hours. This would include any extra paracetamol taken throughout the night. Dosage of paracetamol should not be repeated more frequently than every 4-6 hours. Do not take PANADOL Night for more than 3 consecutive nights without consulting your doctor. Do not use with other antihistamine-containing products, including those used on the skin.
Not for use in children 12 years of age and younger. Hypersensitivity to paracetamol, diphenhydramine hydrochloride or to any of the excipients. Diphenhydramine is contraindicated for use in patients with: Narrow-angle glaucoma Stenosing peptic ulcer Symptomatic prostatic hypertrophy Bladder neck obstruction Pyloroduodenal obstruction Diphenhydramine is contraindicated for use in: Newborns or premature infants Lactating women Patients taking monoamine oxidase inhibitors (MAOls) Refer to "Interactions with other medicines" for additional information.
Paracetamol and diphenhydramine hydrochloride should be used with care in patients with: Impaired hepatic function Impaired renal function 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. Caution should be exercised in patients with epilepsy or seizure disorders, myasthenia gravis, prostatic hypertrophy, urinary retention, asthma, bronchitis and chronic obstructive pulmonary disease (COPD). Diphenhydramine hydrochloride may cause drowsiness and may increase the effects of alcohol. Drowsiness may continue the following day. Those affected should not drive or operate machinery; alcohol should be avoided. Do not take for more than 3 days without consulting a doctor. If symptoms persist, medical advice must be sought. Concurrent use of drugs which cause sedation such as tranquillizers, hypnotics and anxiolytics may cause an increase in sedative effects therefore medical advice should be sought before taking diphenhydramine with such medicines. Avoid use with other antihistamine-containing preparations, including topical antihistamines and cough and cold medicines. Use with caution with monoamine oxidase inhibitors (MAOls) or within 2 weeks of stopping an MAOI. Use with caution with other drugs with antimuscarinic properties (e.g. atropine, tricyclic antidepressants. Use with caution in the elderly, who are more likely to experience adverse effects. Avoid use in elderly patients with confusion. Keep out of sight and reach of children. Refer to "Interactions with other medicines" for additional information.
Use in children and the elderly
Do not use in children under 12 years of age, except on the advice of a doctor. Should not be taken by elderly patients with confusion. Sedating antihistamines may cause confusion and paradoxical excitation in the elderly (see PRECAUTIONS). Children and the elderly may experience paradoxical excitation with diphenhydramine. The elderly are more likely to have central nervous system (CNS) depressive side effects, including confusion. (See contraindications.)
Use in Pregnancy (Category A)
This product should not be used during pregnancy without medical advice. Both paracetamol and diphenhydramine have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed. Use of sedating antihistamines during the third trimester may result in reactions in the newborn or premature neonates.
Use in lactation
PANADOL Night should not be used whilst breast feeding without medical advice. Paracetamol is excreted in small amounts (< 0.2%) in breast milk. Maternal ingestion of paracetamol in usual analgesic doses does not appear to present a risk to the breastfed infant. Diphenhydramine is excreted in breast milk. Therefore it is not recommended for breastfeeding mothers unless the potential benefits to the patient are weighed against the possible risk to the infant.
Effects on ability to drive and use machines
PANADOL Night may cause drowsiness, dizziness, blurred vision, cognitive and psychomotor impairment which can seriously affect the patient's ability to drive or operate machinery. If affected, do not drive or operate machinery.
Paracetamol
Reports of adverse reactions to paracetamol are rare but hypersensitivity including skin rash may occur. Although the following adverse reactions have been reported, a causal relationship to the administration of paracetamol has been neither confirmed nor refuted: dyspepsia, nausea, allergic and haematological reactions. 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/labeled dose and considered attributable are tabulated below by System Organ Class and frequency. The following convention has been utilized for the classification of undesirable effects: very common (<::1/10), common (<::1/100, <1/10), uncommon (<::1/1000, <1/100), rare (<::1/10,000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Post marketing experience
As the adverse reactions identified from post-marketing use are reported voluntarily from a population of uncertain size, the frequency is not known but likely to be very rare.
| Body Svstem | Undesirable effect |
| Blood and lymphatic system disorders | Thrombocytopaenia |
| Immune System disorders | Anaphylaxis. Cutaneous hypersensitivity reactions including skin rashes, angiodema, and Stevens Johnson svndrome |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm in patients sensitive to aspirin and other NSAIDs. |
| Hepatobiliarv disorders | Heoatic dysfunction |
Diphenhydramine
Adverse effects of diphenhydramine hydrochloride may include sedation and the antimuscarinic effects of dry mouth, urinary retention, blurred vision, thickened respiratory tract secretions and chest tightness. Other side effects that may occur occasionally are headache, rashes, cross sensitivity to related drugs, photosensivity, gastrointestinal disturbances and psychomotor Impairment. Dystonic reactions to diphenhydrami ne have been reported. Blood disorders including agranulocytosis, leucopoenia, haemolytic anaemia, though rare, have been reported with antihistamines. Paradoxical stimulation may rarely occur, especially in high doses or in children. Adverse reactions which have been observed in clinical trials and which are considered to be common or very common are listed below by MedDRA System Organ Class.
Post marketing experience
The frequency of other adverse reactions identified during post-marketing use is not known, but these reacti.ons are l1'kel/ to be uncommon or rare.
| Body System | Undesirable effect |
| General disorders and administration site conditions | Common:Fatigue |
| Immune system disorders | Not known:Hypersensitivity reactions including rash, urticaria, dyspnoea and anaioedema |
| Psychiatric disorders | Not known:Confusion *, paradoxical excitation * (e.g. increased energy, restlessness, nervousness) * The elderly are more prone to confusion and paradoxical excitation |
| Nervous system disorders | Common:Sedation, drowsiness, disturbance in attention, unsteadiness, dizziness Not known:Convulsions, headache, oaraesthesia, dvskinesias |
| Eve disorders | Not known:Blurred vision |
| Cardiac disorders | Not known:Tachycardis, paloitation |
| Respiratory, thoracic & mediastinal disorders | Not known:Thickening of bronchial secretions |
| Gastrointestinal disorders | Common:Dry mouth Not known:Gastrointestinal disturbance including nausea, vomitina |
| Musculoskeletal and connective tissue disorders | Not known:Muscle twitching |
| Renal and urinary disorders | Not known:Urinary difficulty, urinary retention |
The following interactions with paracetamol have been noted: Anticoagulant drugs (warfarin) - dosage may require reduction if paracetamol and anticoagulants are taken for a prolonged period of time. Paracetamol absorption is increased by substances that increase gastric emptying, eg metoclopramide. Paracetamol absorption is decreased by substances that decrease gastric emptying, eg propantheline, antidepressants with anticholinergic properties and narcotic analgesics. Paracetamol may increase chloramphenicol concentrations. The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes such as alcohol and anticonvulsant agents. Paracetamol excretion may be affected and plasma concentrations altered when given with probenecid. Colestyramine reduces the absorption of paracetamol if given within 1 hour of paracetamol. The following interactions with diphenhydramine hydrochloride have been noted: Central nervous system (CNS) depressants (alcohol, sedatives, opioid analgesics, hypnotics) - may cause an increase in sedation effects. Monoamine oxidase inhibitors (MAOls) and tricyclic antidepressants (TCAs) - may prolong and intensify the anticholinergic and CNS depressive effects. As diphenhydrami ne has some anficholinergic activity, the effects of some anticholinergic drugs (e.g. atropine, tricyclic antidepressants) may be potentiated. Diphenhydramine is an inhibitor of the cytochrome p450 isoenzyme CYP2D6. Therefore, there may be a potential for interaction with drugs that are primarily metabolised by CYP2D6, such as metoprolol and venlafaxine. Avoid use with other antihistamine-containing preparations including topical preparations and cough and cold medicines.
If an overdose is taken or suspected, immediately contact the Poisons Information Centre 0800 764 766 for advice, or go to a hospital straight away even if you feel well because of the risk of delayed, serious liver damage. Paracetamol overdose may cause liver failure. Diphenhydramine overdose is likely to result in effects similar to those listed under adverse reactions. Additional symptoms may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes. Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse.
Treatment
Paracetamol Immediate medical management is required in the event of overdose, even if symptoms of overdose are not present. Administration of N-acetylcysteine or methionine may be required. Diphenhydramine Treatment should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam.
Shelf-life
24 months from the date of manufacture
Special storage precautions
Store below 30degC. Protect from moisture and keep out of reach of children.
Incompatibilities
Not applicable
Use and handling
No special requirements
Restricted Medicine.
Packs of 20 containing two blisters of 10 caplets each.
There is no further information for PANADOL Night.
GlaxoSmithKline (NZ) Ltd (trading as GlaxoSmithKline Consumer Healthcare) Auckland, New Zealand Telephone: (09) 367 2970
11 May 2012