Midrid Capsules 30s

1. Name Of The Medicinal Product

Midrid Capsules

2. Qualitative And Quantitative Composition

Paracetamol 325.0mg

Isometheptene mucate 65.0mg

3. Pharmaceutical Form

Capsule

4. Clinical Particulars

4.1 Therapeutic Indications

In the treatment of migraine and other vascular headaches

4.2 Posology And Method Of Administration

For oral administration

Adults: 2 capsules at once, then 1 capsule every hour until relief obtained up to a maximum of 5 capsules within a 12 hour period

Children: Not recommended

4.3 Contraindications

Severe cardiac, hepatic or renal impairment, severe hypertension, glaucoma. Patients on monoamine oxidase inhibitor therapy. Porphyria. Hypersensitivity to paracetamol and/or other constituents.

4.4 Special Warnings And Precautions For Use

Cardiovascular disease, diabetes mellitus, hyperthyroidism. When used in patients with high spinal cord lesions, isometheptene, like other sympathomimetics may cause autonomic dysreflexia.

Care is advised in the administration of this product to patients with renal or hepatic impairment. The hazards of paracetamol overdose are greater in those with non-cirrhotic alcoholic liver disease.

Do not exceed the recommended dose

If symptoms persist, consult your doctor

Keep out of the sight and reach of children

Patient information leaflet warning

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

Label warning

Do not take with any other paracetamol-containing products. Immediate medical advice should be sought in the event of an overdose, even if you feel well.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

On theoretical grounds, care should be taken with patients receiving cardiac glycosides, quinidine, anti-hypertensives and tricyclic antidepressants. Alcohol reduces liver capacity to deal with paracetamol. Cholestyramine reduces absorption of paracetamol. Metoclopramide and domperidone accelerate absorption of paracetamol. May interact with chloramphenicol, causing increased plasma levels.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

There is an increased risk of toxicity with bromocriptine and isometheptene.

There is an increased risk of a hypertensive crisis when sympathomimetics are given with MAOIs.

4.6 Pregnancy And Lactation

There is no evidence of the product's safety in human pregnancy nor is there evidence from animal work that it is free from hazard. Avoid in pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

No information

4.8 Undesirable Effects

Transient dizziness may appear in hypersensitive patients. This can usually be eliminated by reducing the dose. Circulatory disturbances may occur.

Adverse effects of paracetamol are rare but hypersensitivity reactions including skin rashes may occur. Anaphylaxis, angioedema, urticaria and very rare cases of fixed drug eruption have been reported. There have been reports of blood dyscrasias including thrombocytopenia, purpura and agranulocytosis, but these were not necessarily causally related to paracetamol.

Blood disorders have also been reported with isometheptene containing products.

4.9 Overdose

Liver damage is possible in adults who have taken 10g or more of paracetamol.

Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

If the patient

a. is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes

or

b. regularly consumes ethanol in excess of recommended amounts

or

c. is likely to be glutathione deplete eg eating disorders, cystic fibrosis, HIV infection, starvation, cachexia

Symptoms

Symptoms of paracetamol overdosage 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.

Management

Immediate treatment is essential in the management of paracetamol overdosage. 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, see BNF overdose section.

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol 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 paracetamol, 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 24 hr from ingestion should be discussed with the NPIS or a liver unit.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Paracetamol is an effective analgesic and antipyretic agent but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood as it is only a weak inhibitor of prostaglandin biosynthesis, but it has been suggested that it is more effective against enzymes in the CNS than those in the periphery. The drug has no effect on the cardiovascular and respiratory systems, and it does not cause gastric irritation or bleeding like salicylates.

5.2 Pharmacokinetic Properties

Isometheptene mucate is rapidly excreted in man. Excretion peaks at 2-6 hours after dosing.

Paracetamol is readily absorbed from the gastrointestinal 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 sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half life varies from about 1 to 4 hours. Plasma-protein blinding 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 paracetamol overdosage and cause liver damage.

5.3 Preclinical Safety Data

There are no other data of relevance to the prescriber which are not included on the SPC

6. Pharmaceutical Particulars

6.1 List Of Excipients

Microcrystalline cellulose

Talc

Colloidal silicon dioxide

Purified water

Capsule shell:

Gelatin

Water

Titanium dioxide

Erythrosine

Quinoline yellow

Indigotine

Printing ink Opacode black S-1-8100HV

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 25°C

6.5 Nature And Contents Of Container

Securitainers of 100 capsules

Strips of 5 or 15 capsules

Blister packs of 5, 10, 15, 20 and 30 capsules

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Manx Healthcare Ltd

Taylor Group House

Wedgnock Lane

Warwick

CV34 5YA

United Kingdom

8. Marketing Authorisation Number(S)

PL 14251/0020

9. Date Of First Authorisation/Renewal Of The Authorisation

18 May 2004 / 19 December 2007

10. Date Of Revision Of The Text

April 2008