Diphenhydramine

Diphenhydramine may potentiate the effects of alcohol and other depressants including opioid analgesics, anticonvulsants, antidepressants, antihistamines, antiemetics, antipsychotics, anxiolytic sedatives and hypnotics.

As diphenhydramine possesses some anticholinergic activity, the effects of anticholinergics (e.g. some psychotropic drugs and atropine) may be potentiated by this product giving rise to in tachycardia, mouth dryness, gastrointestinal disturbances (e.g. colic), urinary retention and headache.

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. Concomitant administration of diphenhydramine with these drugs should be avoided. Diphenhydramine itself is a high affinity substrate of CYP2D6. Therefore, concomitant administration with CYP2D6 inhibitors should be avoided. The administration of diphenhydramine should occur with caution in (very) slow metabolisers.

In patients with moderate to severe renal or hepatic impairment, a lower dose might be required.

Diphenhydramine should be used with caution in patients with myasthenia gravis, epilepsy or seizure disorders, narrow-angle glaucoma, prostatic hypertrophy, urinary retention, asthma, bronchitis, restless leg syndrome and chronic obstructive pulmonary disease (COPD).

There is not adequate data from the use of diphenhydramine in pregnant women. Animal studies are insufficient with respect to effects on pregnancy.

Diphenhydramine crosses the placental barrier and has been reported to cause jaundice and extrapyramidal symptoms in infants whose mothers received the drug during pregnancy.

Use of diphenhydramine during the first trimester of pregnancy has been associated with an increased risk of fetal abnormalities.

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. Patients should consult a doctor before use.

Diphenhydramine has been detected in breast milk, but the effect of this on breastfed infants is unknown. If administered during breastfeeding there is an increased risk of adverse effects of antihistamines, such as unusual excitation or irritability in infants. Diphenhydramine is not recommended whilst breastfeeding without medical advice.

Fertility

There are no available data on the effect of diphenhydramine on fertility.

Diphenhydramine has a major influence on the 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 andpsychomotor impairment. If affected, do not drive or operate machinery.

Diphenhydramine tablet as a symptomatic aid to the relief of temporary sleep disturbance in adults

Specific estimation of the frequency of adverse events for consumer 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 post-marketing use is unknown, but these reactions are likely to be uncommon (occurring in ≥1/1,000 to <1/100) or rare (occurring in ≥1/10,000 to <1/1,000).

Blood and lymphatic system disorders

Rare: Thrombocytopenia

Immune system disorders

Unknown: Hypersensitivity reactions including rash, urticaria, dyspnoea and angioedema

Psychiatric disorders*

Unknown: 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,

Unknown: convulsions, headache, paraesthesia, dyskinesias, restless leg syndrome.

Eye disorders

Unknown: blurred vision

Cardiac disorders

Unknown: tachycardia, palpitations

Respiratory, thoracic and mediastinal disorders

Unknown: thickening of bronchial secretions

Gastrointestinal disorders

Common:dry mouth

Unknown: gastrointestinal disturbance including nausea, vomiting

Musculoskeletal and connective tissue disorders

Unknown: muscle twitching

Renal and urinary disorders

Unknown: urinary difficulty, urinary retention

General disorders and administration site conditions

Common: fatigue

Diphenhydramine syrup in the symptomatic relief of non-productive cough and of allergic conditions and reactions

Data from several clinical trials are available with a total population of 936 people treated with diphenhydramine where adverse events were assessed. Additionally, adverse events reported during post-marketing experience are included.

Post marketing data

Adverse drug reactions (ADRs) identified during post-marketing experience with diphenhydramine/menthol are included in the table below.

The frequencies are provided according to the following convention: Very common (≥1/10); Common (≥1/100 and <1/10); Uncommon (≥1/1,000 and <1/100); Rare (≥1/10,000 and <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

Adverse Drug Reactions Identified During Post-Marketing Experience with
diphenhydramine/menthol, Frequency Category Estimated from Clinical
Trials or Epidemiology Studies*:

^* Frequency category based on clinical trials with single-ingredient diphenhydramine.
^§ Adverse drug reaction only reported in one clinical trial.