Drugs List

Therapeutic Indications

Uses

Relief of migraine and other vascular headaches

Contraindications

Children under 18 years
Glaucoma
Porphyria
Post partum
Severe cardiac dysfunction
Severe hepatic impairment
Severe hypertension
Severe renal impairment

Precautions and Warnings

Breastfeeding
Cardiovascular disorder
Diabetes mellitus
Hepatic impairment
Hyperthyroidism
Non-cirrhotic alcoholic liver disease
Pregnancy
Renal impairment
Spinal cord injury

Overdosage causes liver damage
Seek urgent medical advice in event of overdose, even if patient feels well
Advise patient not to take paracetamol during treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Pregnancy and Lactation

Pregnancy

Use paracetamol and isometheptene mucate with caution in pregnancy.

Their is very little published information of pregnant women taking this medication and so the manufacturer advises that this product should be avoided during pregnancy since due to lack of evidence on the product's safety, and no evidence from animal work that it is free from hazard.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use paracetamol and isometheptene mucate with caution in breastfeeding.

The manufacturer advises that this product should be avoided during lactation since there is a lack of evidence on the product's safety, and no evidence from animal work that it is free from hazard. However Briggs (2015) suggests it could still be taken but other more studied migraine treatments are the prefered option.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute generalised exanthematous pustulosis
Agranulocytosis
Anaphylaxis
Angioedema
Blood disorders
Blood dyscrasias
Circulatory disturbances
Dizziness
Fixed drug eruption
Hypersensitivity reactions
Hypotension
Leucopenia
Methaemoglobinaemia
Neutropenia
Rash
Stevens-Johnson syndrome
Thrombocytopenic purpura
Toxic epidermal necrolysis
Urticaria

Presentation

Capsules containing paracetamol and isometheptene mucate

Drugs List

Therapeutic Indications

Uses

Relief of migraine and other vascular headaches

Dosage

Adults

Elderly

Contraindications

Children under 18 years
Glaucoma
Porphyria
Post partum
Severe cardiac dysfunction
Severe hepatic impairment
Severe hypertension
Severe renal impairment

Precautions and Warnings

Breastfeeding
Cardiovascular disorder
Diabetes mellitus
Hepatic impairment
Hyperthyroidism
Non-cirrhotic alcoholic liver disease
Pregnancy
Renal impairment
Spinal cord injury

Overdosage causes liver damage
Seek urgent medical advice in event of overdose, even if patient feels well
Advise patient not to take paracetamol during treatment
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient to consult a doctor if symptoms persist despite treatment
Patients should not exceed recommended dose

Pregnancy and Lactation

Pregnancy

Use paracetamol and isometheptene mucate with caution in pregnancy.

Their is very little published information of pregnant women taking this medication and so the manufacturer advises that this product should be avoided during pregnancy since due to lack of evidence on the product's safety, and no evidence from animal work that it is free from hazard.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use paracetamol and isometheptene mucate with caution in breastfeeding.

The manufacturer advises that this product should be avoided during lactation since there is a lack of evidence on the product's safety, and no evidence from animal work that it is free from hazard. However Briggs (2015) suggests it could still be taken but other more studied migraine treatments are the prefered option.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute generalised exanthematous pustulosis
Agranulocytosis
Anaphylaxis
Angioedema
Blood disorders
Blood dyscrasias
Circulatory disturbances
Dizziness
Fixed drug eruption
Hypersensitivity reactions
Hypotension
Leucopenia
Methaemoglobinaemia
Neutropenia
Rash
Stevens-Johnson syndrome
Thrombocytopenic purpura
Toxic epidermal necrolysis
Urticaria

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

The MHRA have produced 'generic' overdose sections for the top ten drugs for which the NPIS received the greatest number of queries about management of overdose in 2002. This information is represented below:

Liver damage is possible in patients who have taken 75 mg/kg or more of paracetamol in less than an hour, and these patients should be referred to hospital. To avoid underestimating the potentially toxic paracetamol dose ingested by obese patients who weigh more than 110 kg, a bodyweight of 110 kg (rather than the actual bodyweight) should be used to calculate the total dose of paracetamol ingested in mg/kg.

Signs and 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.

Treatment

Immediate treatment is essential in the management of paracetamol 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 in excess of 150 mg/kg has been taken within 1 hour. Treatment with acetylcysteine is used up to, and possibly beyond, 24 hours of ingesting paracetamol. It is most effective if given within 8 hours of ingestion, after which effectiveness declines. If required, the patient should be given intravenous acetylcysteine, in line with the established dosage schedule. Giving acetylcysteine by mouth (unlicensed route) is an alternative if intravenous access is not possible. Acetylcysteine can be given irrespective of the plasma paracetamol concentration:
in circumstances where the overdose is staggered or there is doubt over the time of paracetamol ingestion; or
in overdose with a timed plasma paracetamol concentration on or above a single treatment line joining points of 100 mg/L at 4 hours and 15 mg/L at 15 hours as shown on the nomogram (https://www.mhra.gov.uk/home/groups/pl-p/documents/drugsafetymessage/con184396.pdf), regardless of risk factors of hepatotoxicity.

Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). If vomiting is not a problem, and overdose has been taken within 10 to 12 hours, oral methionine may be a suitable alternative for remote areas outside hospital. Management of patients who present beyond 24 hours from ingestion or with serious hepatic dysfunction should be discussed with the NPIS (https://www.npis.org/) or a liver unit.

Further Information

Last Full Review Date: June 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 15 June 2016.

Summary of Product Characteristics: Midrid Capsules. DHP Healthcare Ltd. Revised July 2015.

Paracetamol
MHRA 22nd January 2007
Available at: https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: 15 June 2016