Diphenhydramine/ Paracetamol

Registered South African indications:

• Insomnia

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Porphyria
• Antihistamines in premature infants or neonates who have increased susceptibility to antimuscarinic effects

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Epilepsy 
• Seizure disorders
• Prostatic hypertrophy
• Closed angle glaucoma
• Urinary retention
• Pyloroduodenal obstruction
• Asthma
• Bronchitis
• Chronic obstructive pulmonary disease
• Myasthenia gravis
• Non-cirrhotic alcoholic hepatic disease
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsoprtion 
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Insomnia with coexisting pain

Diphenhydramine/ Paracetamol
25/500 (mg)

• Oral (tab): 2 tabs, at bedtime; Max: 2 tabs/24hrs

Not established for use in children below 12 years

Pregnancy

• Caution
• Paracetamol/diphenhydramine should not be used during pregnancy without medical advice. Human and animal studies with paracetamol have not identified any risk to pregnancy or embryo-foetal development
• There are no adequate data from the use of diphenhydramine in pregnant women. Animal studies are insufficient with respects to pregnancy. 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

Breastfeeding

• Caution
• Paracetamol/diphenhydramine should not be used whilst breastfeeding without medical advice. Human studies with paracetamol have not identified any risk to lactation or the breastfed infant. Paracetamol crosses the placental barrier and is excreted in breast milk  
• Diphenhydramine has been detected in breast milk, but the effects of this on breastfed infants are unknown

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended
  Use of low doses for the shortest possible time is recommended; This is usually well tolerated in cirrhosis/hepatic disease
  Chronic use is not recommended; Doses <4g/day have been associated with hepatotoxicity in some cases

Elderly

• Caution; no dose adjustment recommended
  Should not be taken by elderly patients with confusion

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Diphenhydramine
Central Nervous System Disorders

• Sedation
• Disturbances in attention
• Unsteadiness
• Dizziness
• Seizures
• Headache
• Paraesthesia
• Dyskinesias
• Fatigue
• Confusion
• Paradoxical excitement

Cardiovascular Disorders

• Tachycardia
• Palpitations

Respiratory Disorders

• Dyspnoea
• Thickening of bronchial secretions

Gastrointestinal Disorders

• Dry mouth
• Nausea and vomiting

Genitourinary Disorders

• Urinary difficulty
• Urinary retention

Musculoskeletal Disorders

• Muscle twitching

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Urticaria
• Angioedema

Sensory Disorders

• Blurred vision
• Tinnitus

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic dysfunction

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Cutaneous hypersensitivity reactions 
• Angioedema
• Stevens Johnson syndrome
• Thrombocytopenia 
• Agranulocytosis
• Methaemoglobinaemia

• Other antihistamine-containing preparations
• Other paracetamol-containing products
• Central nervous system depressants
• Metoclopramide 
• Domperidone 
• Colestyramine
• Warfarin 
• Monoamine oxidase inhibitors
• Other anticholinergic agents
• CYP2D6 substrates

None routine. Specific cases may require

• Hepatic function 

Diphenhydramine
Diphenhydramine is a histamine H1-receptor antagonist that competes with free histamine for binding at histamine receptors. In addition to its usual anti-allergy actions, it also has significant sedative and antimuscarinic properties.

Paracetamol
Paracetamol increases the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis. It does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects.

COMBINATION PREPARATIONS

Diphenhydramine/ Paracetamol

Tablet 25mg/500mg

• Mypaid Night Pain (Adcock)