Drugs List

Therapeutic Indications

Uses

Migraine (attack)

Contraindications

Children under 18 years
Breastfeeding
Coagulopathy
Duodenal ulcer
Gastric ulcer
Gastrointestinal haemorrhage
Gastrointestinal obstruction
Gastrointestinal perforation
Haemophilia
History of gastrointestinal haemorrhage
History of gastrointestinal ulceration
Phaeochromocytoma
Phenylketonuria
Third trimester of pregnancy
Within 4 days of gastrointestinal surgery

Precautions and Warnings

Atopy
Elderly
High alcohol intake
Young adults
Allergic rhinitis
Asthma
Epileptic disorder
First trimester of pregnancy
Gout
Hepatic impairment
Menorrhagia
Nasal polyps
Renal impairment
Second trimester of pregnancy

Contains aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Discontinue therapy immediately & permanently if methaemoglobinaemia occurs
May cause extrapyramidal effects in the elderly and young adults
Discontinue if patient develops neuroleptic malignant syndrome
Duration of use should not exceed 3 months
Advise patient to consult doctor before any self medication
Advise patient concurrent alcohol will increase drowsiness

If vomiting persists, reassess for possibility of underlying disorders e.g. cerebral irritation.

Treatment should not exceed three months due to the risk of tardive dyskinesia with metoclopramide.

High doses of metoclopramide result in extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion and hallucination occurring more frequently. Young adults and elderly patients are at increased risk of extrapyramidal reactions. Symptomatic treatment may be necessary.

Advise patients to consult their doctor or pharmacist before taking over the counter NSAIDs or antacids as these may affect salicylate blood concentration and antihistamines which may increase drowsiness.

Owing to the association with Reye's syndrome, the CSM has advised that aspirin containing preparations should not be given to children and adolescents under 16 years unless specifically indicated for Kawasaki syndrome.

Pregnancy and Lactation

Pregnancy

DL-lysine acetylsalicylate and metoclopramide hydrochloride is contraindicated in the third trimester of pregnancy, and should be used with caution during the first and second trimesters.

Aspirin
This medication should be used with extreme caution during the first and second trimester. This product should not be used during the third trimester. Aspirin has been used for many years during pregnancy, however, the safety of aspirin in pregnancy is still under question. Aspirin crosses the placenta and can accumulate in the foetus due to slow elimination by the foetus. Briggs (2011) states that aspirin used near term may prolong gestation and labour, and increase the risk of haemorrhage during delivery. Premature closure of the ductus arteriosus may occur if aspirin is used late in the pregnancy, with the possibility of the associated complication of persistent pulmonary hypertension of the newborn. Therefore, this product is contraindicated during the third trimester and extreme caution is advised if this product is to be used during the first and second trimesters.

Metoclopramide
Metoclopramide has been used for many years as a treatment for nausea and vomiting during pregnancy and both Briggs (2011) and Schaefer (2007) consider it to be safe as a single agent.

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

DL-lysine acetylsalicylate and metoclopramide hydrochloride is contraindicated in breastfeeding.

Aspirin and metoclopramide are excreted in breast milk and adverse reactions in the breastfed infant cannot be excluded.

Aspirin
The medication is contraindicated while breastfeeding. Aspirin in excreted in breast milk in small amounts, although aspirin clearance from breast milk is slower than that from plasma. High doses of aspirin present a potential risk to the infants platelet function. There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. Aspirin is associated with significant effects on some nursing infants and should be given to nursing mothers with caution. However, Schaefer (2007) suggest that aspirin should not be used chronically in nursing mothers.

Metoclopramide
Metoclopramide increases the secretion of prolactin and hence increases milk production. Despite being secreted into breast milk with a milk:plasma ratio of 1.8 to 1.9, there are only few reports of mild adverse effects in nursing infants. Briggs (2011), Schaefer (2007) and Hale (2010) consider its use to be safe for appropriate indications.

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 dystonias
Agranulocytosis
Akathisia
Amenorrhoea
Anaphylaxis
Anxiety
Asthenia
Bradycardia
Bronchospasm
Bulbar type of speech
Colitis
Confusion
Depression
Diarrhoea
Dizziness
Drowsiness
Dyskinesia
Dyspepsia
Erosive duodenitis
Extra-ocular muscle spasm
Facial muscle spasm
Flatulence
Galactorrhoea
Gastric irritation
Gastric ulceration
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gynaecomastia
Haemolytic anaemia
Hallucinations
Heart block
Hyperprolactinaemia
Hypersensitivity reactions
Hypothrombinaemia
Impaired consciousness
Increase in muscle tone
Inhibition of platelet aggregation
Insomnia
Iron deficiency anaemia
Lethargy
Methaemoglobinaemia
Nausea
Neuroleptic malignant syndrome
Oculogyric crisis
Oesophageal ulceration
Oesophagitis
Opisthotonos
Parkinsonism
Prothrombin time increased
Restlessness
Rhythmic protrusion of tongue
Seizures
Sulfaemoglobinaemia
Tardive dyskinesia
Thrombocytopenia
Tinnitus
Trismus
Unnatural positioning of head and shoulders
Urate kidney stones
Urticaria
Vomiting

Presentation

Sachets containing DL-lysine acetylsalicylate and metoclopramide hydrochloride

Drugs List

Therapeutic Indications

Uses

Migraine (attack)

Dosage

Adults

Elderly

Patients with Renal Impairment

Contraindications

Children under 18 years
Breastfeeding
Coagulopathy
Duodenal ulcer
Gastric ulcer
Gastrointestinal haemorrhage
Gastrointestinal obstruction
Gastrointestinal perforation
Haemophilia
History of gastrointestinal haemorrhage
History of gastrointestinal ulceration
Phaeochromocytoma
Phenylketonuria
Third trimester of pregnancy
Within 4 days of gastrointestinal surgery

Precautions and Warnings

Atopy
Elderly
High alcohol intake
Young adults
Allergic rhinitis
Asthma
Epileptic disorder
First trimester of pregnancy
Gout
Hepatic impairment
Menorrhagia
Nasal polyps
Renal impairment
Second trimester of pregnancy

Contains aspartame - caution in phenylketonuria
Advise ability to drive/operate machinery may be affected by side effects
Discontinue therapy immediately & permanently if methaemoglobinaemia occurs
May cause extrapyramidal effects in the elderly and young adults
Discontinue if patient develops neuroleptic malignant syndrome
Duration of use should not exceed 3 months
Advise patient to consult doctor before any self medication
Advise patient concurrent alcohol will increase drowsiness

If vomiting persists, reassess for possibility of underlying disorders e.g. cerebral irritation.

Treatment should not exceed three months due to the risk of tardive dyskinesia with metoclopramide.

High doses of metoclopramide result in extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion and hallucination occurring more frequently. Young adults and elderly patients are at increased risk of extrapyramidal reactions. Symptomatic treatment may be necessary.

Advise patients to consult their doctor or pharmacist before taking over the counter NSAIDs or antacids as these may affect salicylate blood concentration and antihistamines which may increase drowsiness.

Owing to the association with Reye's syndrome, the CSM has advised that aspirin containing preparations should not be given to children and adolescents under 16 years unless specifically indicated for Kawasaki syndrome.

Pregnancy and Lactation

Pregnancy

DL-lysine acetylsalicylate and metoclopramide hydrochloride is contraindicated in the third trimester of pregnancy, and should be used with caution during the first and second trimesters.

Aspirin
This medication should be used with extreme caution during the first and second trimester. This product should not be used during the third trimester. Aspirin has been used for many years during pregnancy, however, the safety of aspirin in pregnancy is still under question. Aspirin crosses the placenta and can accumulate in the foetus due to slow elimination by the foetus. Briggs (2011) states that aspirin used near term may prolong gestation and labour, and increase the risk of haemorrhage during delivery. Premature closure of the ductus arteriosus may occur if aspirin is used late in the pregnancy, with the possibility of the associated complication of persistent pulmonary hypertension of the newborn. Therefore, this product is contraindicated during the third trimester and extreme caution is advised if this product is to be used during the first and second trimesters.

Metoclopramide
Metoclopramide has been used for many years as a treatment for nausea and vomiting during pregnancy and both Briggs (2011) and Schaefer (2007) consider it to be safe as a single agent.

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

DL-lysine acetylsalicylate and metoclopramide hydrochloride is contraindicated in breastfeeding.

Aspirin and metoclopramide are excreted in breast milk and adverse reactions in the breastfed infant cannot be excluded.

Aspirin
The medication is contraindicated while breastfeeding. Aspirin in excreted in breast milk in small amounts, although aspirin clearance from breast milk is slower than that from plasma. High doses of aspirin present a potential risk to the infants platelet function. There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. Aspirin is associated with significant effects on some nursing infants and should be given to nursing mothers with caution. However, Schaefer (2007) suggest that aspirin should not be used chronically in nursing mothers.

Metoclopramide
Metoclopramide increases the secretion of prolactin and hence increases milk production. Despite being secreted into breast milk with a milk:plasma ratio of 1.8 to 1.9, there are only few reports of mild adverse effects in nursing infants. Briggs (2011), Schaefer (2007) and Hale (2010) consider its use to be safe for appropriate indications.

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

Counselling

May cause drowsiness, do not drive or operate machinery if affected.

Advise patients that drowsiness may be potentiated by CNS depressants or alcohol.

Advise patients to completely dissolve the contents of the sachet in water before taking.

Advise patients not to take more than 3 sachets in 24 hours.

Advise patients to consult their doctor or pharmacist before taking over the counter NSAIDs or antacids as these may affect salicylate blood concentration and antihistamines which may increase drowsiness.

Side Effects

Acute dystonias
Agranulocytosis
Akathisia
Amenorrhoea
Anaphylaxis
Anxiety
Asthenia
Bradycardia
Bronchospasm
Bulbar type of speech
Colitis
Confusion
Depression
Diarrhoea
Dizziness
Drowsiness
Dyskinesia
Dyspepsia
Erosive duodenitis
Extra-ocular muscle spasm
Facial muscle spasm
Flatulence
Galactorrhoea
Gastric irritation
Gastric ulceration
Gastritis
Gastro-intestinal disturbances
Gastro-intestinal haemorrhage
Gastro-intestinal perforation
Gastro-intestinal ulceration
Gynaecomastia
Haemolytic anaemia
Hallucinations
Heart block
Hyperprolactinaemia
Hypersensitivity reactions
Hypothrombinaemia
Impaired consciousness
Increase in muscle tone
Inhibition of platelet aggregation
Insomnia
Iron deficiency anaemia
Lethargy
Methaemoglobinaemia
Nausea
Neuroleptic malignant syndrome
Oculogyric crisis
Oesophageal ulceration
Oesophagitis
Opisthotonos
Parkinsonism
Prothrombin time increased
Restlessness
Rhythmic protrusion of tongue
Seizures
Sulfaemoglobinaemia
Tardive dyskinesia
Thrombocytopenia
Tinnitus
Trismus
Unnatural positioning of head and shoulders
Urate kidney stones
Urticaria
Vomiting

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 attached below:

Salicylate poisoning is usually associated with plasma concentrations above 350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (95.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.

Signs and Symptoms

Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH (normal or reduced hydrogen ion concentration) is usual in adults and children over the age of four years. In children aged four years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

Treatment

Give activated charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations above 700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

Further Information

Last Full Review Date: February 2014

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press https://www.medicinescomplete.com [Accessed on February 19, 2014].

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas

Summary of Product Characteristics: MigraMax. Zentiva. Revised September 2013.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

MHRA 22nd January 2007
https://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Informationforlicenceapplicants/Guidance/OverdosesectionsofSPCs/Genericoverdosesections/index.htm
Last accessed: February 19, 2014