Summary of product characteristics
1. Name of the medicinal product
When sold as an antihistamine :
Histergan Tablets
When sold as a sleep aid:
Paxidorm Tablets 25mg
Numark Night Time Sleep Aid Tablets
NightAid
Aspar Sleep Aid 25 mg Tablets
Tor Generics Sleep Aid 25mg Tablets
Oberon Sleep Aid 25mg Tablets
EM Pharma Sleep Aid 25mg Tablets
2. Qualitative and quantitative composition
Diphenhydramine Hydrochloride 25mg
Excipients with known effects:
Lactose
Sucrose
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Pink sugar coated tablets
4.1. Therapeutic indications
As an antihistamine:
Treatment of allergic conditions e.g. hay fever, vasomotor rhinitis, stings, urticaria, angioneurotic oedema, drug sensitivity, contact dermatitis and photosensitivity.
As a sleep aid:
As a short term hypnotic.
4.2. Posology and method of administration
As an antihistamine:
Adults and Children over 12 years: 1 or 2 tablets three or four times per day. In severe or chronic conditions this may be increased at the discretion of a doctor, but not to exceed 300mg in any 24 hour period.
Paediatric Population:
Not recommended for children under the age of 12.
Elderly: As for adults, use cautiously, reduce dose if required.
As a sleep aid:
Adults: 1 or 2 tablets at bedtime, or after retiring when sleep is not readily achieved
Paediatric Population:
Not recommended for children under the age of 16
Elderly: As for adults, use cautiously, reduce dose if required.
4.3. Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Contraindicated for use in patients with the following conditions: stenosing peptic ulcer, pyloroduodenal obstruction.
When used as a sleep aid: Sedation of children under the age of 16 should only be under medical direction, consequently use as a sedative in this age group is contraindicated.
4.4. Special warnings and precautions for use
Diphenhydramine should be used with caution in patients with myasthenia gravis,epilepsy or seizure disorders, prostatic hypertrophy, urinary retention, narrow-angle glaucoma, asthma, bronchitis and chronic obstructive pulmonary disease (COPD), moderate to severe hepatic impairment and moderate to severe renal impairment.
Tolerance may develop with continuous use. Seek medical advice if sleeplessness persists, as insomnia may be a symptom of a serious underlying medical illness.
May increase the effects of alcohol, therefore alcohol should be avoided. Avoid use of other antihistamine-containing preparations, including topical antihistamines and cough and cold medicines.
Use with caution in the elderly, who are more likely to experience side-effects. Avoid use in elderly patients with confusion.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5. Interaction with other medicinal products and other forms of interaction
Diphenhydramine may potentiate the sedative effects of alcohol and other CNS depressants (e.g. tranquillizers, hypnotics and anxiolytics).
Monoamine oxidase inhibitors (MAOIs) prolong and intensify the anticholinergic effects of diphenhydramine. The product should be used with caution with MAOIs or within 2 weeks of stopping an MAOI.
As diphenhydramine has some antimuscarinic activity, the effects of some anticholinergic drugs (e.g. atropine, tricyclic antidepressants) may be potentiated therefore medical advice should be sought before taking diphenhydramine with such medicines.
Diphenhydramine is an inhibitor of the cytochrome p450 isoenzyme CYP2D6. Therefore, there may be a potential for interaction with drugs which are primarily metabolised by CYP2D6, such as metoprolol and venlafaxine.
Diphenhydramine should not be used in patients receiving any of the above drugs unless directed by a doctor
4.6. Fertility, pregnancy and lactation
Pregnancy
Diphenhydramine crosses the placenta. Because animal reproduction studies are not always predictive of human response and since there is inadequate experience with use of diphenhydramine in pregnant women, the potential risk for humans is unknown. Use of sedating antihistamines during the third trimester may result in reactions in the newborn or premature neonates. This drug is not recommended during pregnancy. Consult a doctor before use.
Lactation
Diphenhydramine has been detected in breast milk, but the effect of this on breastfed infants is unknown. Diphenhydramine is not recommended for use during lactation. Consult a doctor before use.
4.7. Effects on ability to drive and use machines
Diphenhydramine is a hypnotic and will produce drowsiness or sedation soon after the dose has been taken. It may also cause dizziness, blurred vision, cognitive and psychomotor impairment. These can seriously affect the patient's ability to drive and use machines. If affected, do not drive or operate machinery.
4.8. Undesirable effects
Specific estimation of the frequency of adverse events for OTC products is inherently difficult (particularly numerator data). Adverse reactions which have been observed in clinical trials and which are considered to be common (occurring in >1/100 to <1/10) or very common (occurring in >1/10) are listed below by MedDRA System Organ Class. The frequency of other adverse reactions identified during postmarketing use is unknown, but these reactions are likely to be uncommon (occurring in >1/1,000 to <1/100) or rare (occurring in <1/1000).
| System Organ Class
| Very Common
(≥1/10)
| Common
≥1/100, < 1/10
| Uncommon
≥1/1,000, <1/100
| Rare
≥1/10,000, <1/1000
| Very Rare
<1/10,000
| Not known (cannot be estimated from available data)
|
| Cardiac Disorders
|
|
|
|
|
| tachycardia, palpitations, arrhythmias
|
| Eye Disorders
|
|
|
|
|
| blurred vision
|
| General disorders and administration site conditions:
|
| fatigue
|
|
|
|
|
| Gastrointestinal Disorders
|
| dry mouth
|
|
|
| gastrointestinal disturbance including nausea, vomiting
|
| Immune System Disorders
|
|
|
|
|
| hypersensitivity reactions including rash, urticaria, dyspnoea and angioedema
|
| Musculoskeletal and connective tissue Disorders
|
|
|
|
|
| muscle twitching
|
| Nervous System Disorders
|
| sedation, drowsiness, disturbance in attention, unsteadiness, dizziness
|
|
|
| convulsions, headache, paraesthesia, dyskinesias
|
| Psychiatric Disorders
|
|
|
|
|
| confusion, paradoxical excitation (e.g. increased energy, restlessness, nervousness), depression, sleep disturbances * The elderly are more prone to confusion and paradoxical excitation.
|
| Renal and urinary disorders
|
|
|
|
|
| urinary difficulty, urinary retention
|
| Respiratory, thoracic and mediastinal disorders
|
|
|
|
|
| thickening of bronchial secretions
|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9. Overdose
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 should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam
5.1. Pharmacodynamic properties
Pharmacotherapeutic group: Antihistamines for systemic use – diphenhydramine, ATC Code: R06AA02.
Diphenhydramine is an ethanolamine-derivative anti-histamine with anti-cholinergic (anti-spasmodic), anti-tussive and sedative activity. It acts by inhibiting the effects on H1-receptors.
Diphenhydramine is effective in reducing sleep onset (ie, time to fall asleep) and increasing the depth and quality of sleep.
5.2. Pharmacokinetic properties
Diphenhydramine is a histamine H1 receptor antagonist.
The main site of metabolism is the liver.
Absorption
Diphenhydramine hydrochloride is rapidly absorbed following oral administration. Apparently it undergoes first-pass metabolism in the liver and only about 40-60% of an oral dose reaches systematic circulation as unchanged diphenhydramine.
Distribution
Diphenhydramine is rapidly distributed throughout the whole body. Peak plasma concentrations are attained within 1-4 hours. The sedative effect also appears to be maximal within 1-3 hours after administration of a single dose. It is positively correlated with the plasma drug concentration.
Biotransformation
Diphenhydramine is approx 80-85% bound to plasma proteins. Diphenhydramine is rapidly and almost completely metabolised. It is metabolised principally to diphenylmetoxyacetic acid and is also dealkylated. The metabolites are conjugated with glycine and glutamine and excreted in urine. Only about 1% of a single dose is excreted unchanged in urine.
Elimination
The elimination half-life ranges from 2.4-9.3 hours in healthy adults. The terminal elimination half-life is prolonged in liver cirrhosis.
5.3. Preclinical safety data
Not applicable.
6.1. List of excipients
Lactose, corn starch, povidone, magnesium stearate, Opaseal (polyvinyl acetate phthalate, ethyl acetate and stearic acid), sucrose, calcium carbonate, talc, acacia, titanium dioxide E171, Opalux Pink AS 1537 (E127 erythrosine), Opaglos 6000 (carnauba wax, beeswax), silicone fluid.
6.2. Incompatibilities
Incompatible with barbiturates and iodo compounds in solution.
6.3. Shelf life
36 months
6.4. Special precautions for storage
Store below 25°C.
6.5. Nature and contents of container
Blister packs of 8, 16 and 20 tablets.
6.6. Special precautions for disposal and other handling
None stated
7. Marketing authorisation holder
Norma Chemicals Ltd.
51-53 Stert Street
Abingdon
Oxfordshire OX14 3JF United Kingdom
8. Marketing authorisation number(s)
PL 00386/5008R
9. Date of first authorisation/renewal of the authorisation
08 September 1989 / 14 June 1995
10. Date of revision of the text
13th October 2017
4.1 Therapeutic indications
As an antihistamine:
Treatment of allergic conditions e.g. hay fever, vasomotor rhinitis, stings, urticaria, angioneurotic oedema, drug sensitivity, contact dermatitis and photosensitivity.
As a sleep aid:
As a short term hypnotic.
4.2 Posology and method of administration
As an antihistamine:
Adults and Children over 12 years: 1 or 2 tablets three or four times per day. In severe or chronic conditions this may be increased at the discretion of a doctor, but not to exceed 300mg in any 24 hour period.
Paediatric Population:
Not recommended for children under the age of 12.
Elderly: As for adults, use cautiously, reduce dose if required.
As a sleep aid:
Adults: 1 or 2 tablets at bedtime, or after retiring when sleep is not readily achieved
Paediatric Population:
Not recommended for children under the age of 16
Elderly: As for adults, use cautiously, reduce dose if required.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Contraindicated for use in patients with the following conditions: stenosing peptic ulcer, pyloroduodenal obstruction.
When used as a sleep aid: Sedation of children under the age of 16 should only be under medical direction, consequently use as a sedative in this age group is contraindicated.
4.4 Special warnings and precautions for use
Diphenhydramine should be used with caution in patients with myasthenia gravis,epilepsy or seizure disorders, prostatic hypertrophy, urinary retention, narrow-angle glaucoma, asthma, bronchitis and chronic obstructive pulmonary disease (COPD), moderate to severe hepatic impairment and moderate to severe renal impairment.
Tolerance may develop with continuous use. Seek medical advice if sleeplessness persists, as insomnia may be a symptom of a serious underlying medical illness.
May increase the effects of alcohol, therefore alcohol should be avoided. Avoid use of other antihistamine-containing preparations, including topical antihistamines and cough and cold medicines.
Use with caution in the elderly, who are more likely to experience side-effects. Avoid use in elderly patients with confusion.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Diphenhydramine may potentiate the sedative effects of alcohol and other CNS depressants (e.g. tranquillizers, hypnotics and anxiolytics).
Monoamine oxidase inhibitors (MAOIs) prolong and intensify the anticholinergic effects of diphenhydramine. The product should be used with caution with MAOIs or within 2 weeks of stopping an MAOI.
As diphenhydramine has some antimuscarinic activity, the effects of some anticholinergic drugs (e.g. atropine, tricyclic antidepressants) may be potentiated therefore medical advice should be sought before taking diphenhydramine with such medicines.
Diphenhydramine is an inhibitor of the cytochrome p450 isoenzyme CYP2D6. Therefore, there may be a potential for interaction with drugs which are primarily metabolised by CYP2D6, such as metoprolol and venlafaxine.
Diphenhydramine should not be used in patients receiving any of the above drugs unless directed by a doctor
4.6 Fertility, pregnancy and lactation
Pregnancy
Diphenhydramine crosses the placenta. Because animal reproduction studies are not always predictive of human response and since there is inadequate experience with use of diphenhydramine in pregnant women, the potential risk for humans is unknown. Use of sedating antihistamines during the third trimester may result in reactions in the newborn or premature neonates. This drug is not recommended during pregnancy. Consult a doctor before use.
Lactation
Diphenhydramine has been detected in breast milk, but the effect of this on breastfed infants is unknown. Diphenhydramine is not recommended for use during lactation. Consult a doctor before use.
4.7 Effects on ability to drive and use machines
Diphenhydramine is a hypnotic and will produce drowsiness or sedation soon after the dose has been taken. It may also cause dizziness, blurred vision, cognitive and psychomotor impairment. These can seriously affect the patient's ability to drive and use machines. If affected, do not drive or operate machinery.
4.8 Undesirable effects
Specific estimation of the frequency of adverse events for OTC products is inherently difficult (particularly numerator data). Adverse reactions which have been observed in clinical trials and which are considered to be common (occurring in >1/100 to <1/10) or very common (occurring in >1/10) are listed below by MedDRA System Organ Class. The frequency of other adverse reactions identified during postmarketing use is unknown, but these reactions are likely to be uncommon (occurring in >1/1,000 to <1/100) or rare (occurring in <1/1000).
| System Organ Class
| Very Common
(≥1/10)
| Common
≥1/100, < 1/10
| Uncommon
≥1/1,000, <1/100
| Rare
≥1/10,000, <1/1000
| Very Rare
<1/10,000
| Not known (cannot be estimated from available data)
|
| Cardiac Disorders
|
|
|
|
|
| tachycardia, palpitations, arrhythmias
|
| Eye Disorders
|
|
|
|
|
| blurred vision
|
| General disorders and administration site conditions:
|
| fatigue
|
|
|
|
|
| Gastrointestinal Disorders
|
| dry mouth
|
|
|
| gastrointestinal disturbance including nausea, vomiting
|
| Immune System Disorders
|
|
|
|
|
| hypersensitivity reactions including rash, urticaria, dyspnoea and angioedema
|
| Musculoskeletal and connective tissue Disorders
|
|
|
|
|
| muscle twitching
|
| Nervous System Disorders
|
| sedation, drowsiness, disturbance in attention, unsteadiness, dizziness
|
|
|
| convulsions, headache, paraesthesia, dyskinesias
|
| Psychiatric Disorders
|
|
|
|
|
| confusion, paradoxical excitation (e.g. increased energy, restlessness, nervousness), depression, sleep disturbances * The elderly are more prone to confusion and paradoxical excitation.
|
| Renal and urinary disorders
|
|
|
|
|
| urinary difficulty, urinary retention
|
| Respiratory, thoracic and mediastinal disorders
|
|
|
|
|
| thickening of bronchial secretions
|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
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Drug Licencing
Drugs appearing in this section are approved by UK Medicines & Healthcare Products Regulatory Agency (MHRA), & the European Medicines Agency (EMA).