COMPOSITION: Each film coated tablet contains:
Composition of active ingredients:
Acetaminophen………………………….. 500 mg
Diphenhydramine hydrochloride…… 25 mg
Composition of excipients: Maize starch, pregelatinized starch, povidone K30, colloidal anhydrous silica, sodium starch glycolate, gelatin, talc, magnesium stearate, opadry II white, opadry II blue.
DOSAGE FORM:
Blue, oblong shaped, film coated tablet, biconvex and printed with the “Tydol PM” in black on both sides, tablet is intact.
INDICATIONS:
For the relief of pains:
– rheumatic, muscle pain, backache,
– neuralgia, toothache,
– headache, migraine,
– period pain.
DOSAGE AND ADMINISTRATION:
Administration: For oral administration. Do not exceed the stated dose or frequency of dosing.
Dosage
Adults (including the elderly) and children aged 16 years and over:
Two tablets to be taken 20 minutes before bedtime. Maximum daily dose: Two tablets (1000 mg acetaminophen, 50 mg diphenhydramine hydrochloride) in 24 hours. Other products containing acetaminophen may be taken for daytime pain relief but at a reduced maximum dose of 6 tablets in 24 hours. The dose should not be repeated more frequently than every four hours.
Not recommended for children under 16 years of age except on medical advice.
Patients should not take the tablets for more than 7 consecutive nights without consulting their doctor.
CONTRAINDICATIONS:
– Hypersensitivity to acetaminophen, diphenhydramine hydrochloride or any other excipients of this medicine.
– Porphyria
– Premature infants or neonates.
WARNINGS AND PRECAUTIONS FOR USE:
Special precaution and warning when using medication containing acetaminophen: The doctor must warn the patients about the symptoms of serious skin reactions, can cause death including: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or Lyell syndrome, acute generalized exanthematous pustulosis (AGEP).
Antihistamines should be used with caution in conditions such as epilepsy or seizure disorders, prostatic hypertrophy, narrow-angle glaucoma, urinary retention, pyloroduodenal obstruction, asthma, bronchitis, chronic obstructive pulmonary disease (COPD) or myasthenia gravis. Patients with renal or hepatic impairment should consult their doctor before using this medicine. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.
Avoid use of other antihistamine-containing preparations, including topical antihistamine and cough and cold medicines.
Patients should be advised to consult their doctor if their headaches become persistent.
Patients should be advised not to take other acetaminophen containing products, other drugs with sedating properties, or alcohol concurrently.
May cause drowsiness.
If symptoms persist for more than 7 days medical advice should be sought.
Use with caution in the elderly as they may be more susceptible to adverse effects. Avoid use in elderly with confusion.
PREGNANCY AND LACTATION:
Pregnancy:
This product should not be used during pregnancy without medical advice.
Human and animal studies with acetaminophen 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.
Lactation:
This product should not be used whilst breast feeding without medical advice. Human studies with acetaminophen have not identified any risk to lactation or the breast-fed offspring. Acetaminophen crosses the placental barrier and is excreted in breast milk. Diphenhydramine has been detected in breast milk, but the effects of this on breast-fed infants are unknown.
EFFECTS ON ABILITY TO DRIVE AND OPERATE MACHINERY:
May cause drowsiness, dizziness, blurred vision, cognitive and psychomotor impairment, which can seriously affect patients’ ability to drive and use machinery. If affected they should not drive or operate machinery.
INTERACTIONS AND INCOMPATIBILITIES:
Interactions:
Acetaminophen
Cholestyramine: The speed of absorption of acetaminophen is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.
Metoclopramide and domperidone: The absorption of acetaminophen is increased by metoclopramide and domperidone. However, concurrent use need not be avoided.
Warfarin: The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of acetaminophen with increased risk of bleeding; occasional doses have no significant effect.
Chloramphenicol: Increased plasma concentration of chloramphenicol.
Diphenhydramine hydrochloride
Diphenhydramine may potentiate the sedative effects of alcohol and other CNS depressants (e.g. tranquillizers, hypnotics and anxiolytics).
Monoamine oxidase inhibitors (MAOI) 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.
Incompatibilities:
Not applicable
SIDE EFFECTS:
Acetaminophen
Not known
Blood and lymphatic system: Thrombocytopenia, agranulocytosis
Immune system: Anaphylaxis, cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome/toxic epidermal necrolysis.
Respiratory, thoracic and mediastinal: Bronchospasm
Hepatobiliary: Hepatic dysfunction
Diphenhydramine hydrochloride
Common, 1/100 ≤ ADR < 1/10:
General: Fatigue
Nervous system: Sedation, drowsiness, disturbance in attention, unsteadiness, dizziness
Gastrointestinal: Dry mouth
Not known
Immune system: Hypersensitivity reactions including rash, urticaria, dyspnoea and angioedema
Psychiatric: Confusion, paradoxical excitation (eg increased energy, restlessness, nervousness)
Nervous system: Convulsions, headache, paraesthesia, dyskinesias
Eye: Blurred vision
Cardiac: Tachycardia, palpitations
Respiratory, thoracic and mediastinal: Thickening of bronchial secretions
Gastrointestinal: Gastrointestinal disturbance, including nausea, vomiting
Musculoskeletal and connective tissue: Muscle twitching
Renal and urinary: Urinary difficulty, urinary retention
Immediately inform doctors or physicians on any adverse drug reactions happened when using this drug.
OVERDOSE AND TREATMENT:
Acetaminophen
Liver damage is possible in adults who have taken 10 g or more of acetaminophen. Ingestion of 5 g or more of acetaminophen may lead to liver damage if the patient has risk factors including:
- On long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John’s Wort or other drugs that induce liver enzymes.
- Or regularly consumes ethanol in excess of recommended amounts.
- Or likely to be glutathione deplete such as having eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.
Symptoms
Symptoms of acetaminophen overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Treatment
Immediate treatment is essential in the management of acetaminophen overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines.
Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma acetaminophen concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of acetaminophen, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with a liver unit.
Diphenhydramine hydrochloride
Symptoms
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
Treatment should be supportive and directed towards specific symptoms. Convulsions and marked CNS stimulation should be treated with parenteral diazepam.
PHARMACODYNAMICS:
Pharmacotherapeutic group: Acetaminophen, combinations excl. psycholeptics
ATC code: N02BE51
Acetaminophen
Analgesic – the mechanism of analgesic action has not been fully determined. acetaminophen may act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and to a lesser extent, through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.
Antipyretic – Acetaminophen probably produces antipyresis by acting centrally on the hypothalamic heat-regulation centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus.
Diphenhydramine hydrochloride
Diphenhydramine is an ethanolamine-derivative antihistamine. It is an antihistamine with anticholinergic and marked sedative effects. 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.
PHARMACOKINETICS:
Acetaminophen
Acetaminophen is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as the glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged acetaminophen. The elimination half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.
A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following acetaminophen overdosage and cause liver damage.
Diphenhydramine hydrochloride
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.
It 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.
Diphenhydramine is approx 80-85% bound to plasma proteins. Diphenhydramine is rapidly and almost completely metabolised. The drug 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.
The elimination half-life ranges from 2.4-9.3 hours in healthy adults. The terminal elimination half-life is prolonged in liver cirrhosis.
DESCRIPTION OF PACKAGING:
Box of 10 blisters x 10 film coated tablets.
STORAGE, SHELF-LIFE, SPECIFICATION OF DRUG:
Storage: Store at temperature below 300C, in a dry place, protect from light.
Shelf-life: 36 months from manufacturing date. Do not use after expiry date.
Specification of drug: Manufacturer’s
