Migraleve Pink film-Coated Tablets

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Summary of Product Characteristics last updated on medicines.ie: 21/10/2019

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Johnson & Johnson (Ireland) Ltd

Johnson & Johnson (Ireland) Ltd

Company Products

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Medicine Name ACTIFED 60 mg / 2.5 mg Tablets Active Ingredients Pseudoephedrine Hydrochloride, triprolidine hydrochloride
Medicine Name Arret 2mg Hard Capsules Active Ingredients Loperamide Hydrochloride
Medicine Name Benylin Children's Chesty Coughs Active Ingredients Guaifenesin
Medicine Name Benylin Children's Dry Coughs Active Ingredients Diphenhydramine Hydrochloride, Levomenthol
Medicine Name Benylin Cough Medicine Syrup Active Ingredients Diphenhydramine Hydrochloride, Levomenthol
Medicine Name Benylin Day and Night Tablets Active Ingredients Diphenhydramine Hydrochloride, Paracetamol, Pseudoephedrine Hydrochloride
Medicine Name Benylin Dry Coughs Syrup Active Ingredients Dextromethorphan Hydrobromide, Diphenhydramine Hydrochloride, Levomenthol
Medicine Name Benylin Dual Action Dry Syrup Active Ingredients Dextromethorphan Hydrobromide, Pseudoephedrine Hydrochloride, triprolidine hydrochloride
Medicine Name Benylin Four Flu Tablets Active Ingredients Diphenhydramine Hydrochloride, Paracetamol, Pseudoephedrine Hydrochloride
Medicine Name Benylin Non- Drowsy for Chesty Coughs Active Ingredients Guaifenesin, Levomenthol
Medicine Name BENYLIN Non-Drowsy Dry Coughs, Syrup Active Ingredients Dextromethorphan Hydrobromide
Medicine Name Benylin Phlegm Cough plus Decongestant Syrup Active Ingredients Guaifenesin, Pseudoephedrine Hydrochloride
Medicine Name Benylin Phlegm Cough Syrup Active Ingredients Guaifenesin, Levomenthol
Medicine Name Calpol 120mg/5ml Infant Oral Suspension Active Ingredients Paracetamol
Medicine Name Calpol Infant 120mg/5ml Sugar Free Oral Suspension (bottle) Active Ingredients Paracetamol
Medicine Name Calpol Infant 120mg/5ml Sugar Free Oral Suspension (sachets) Active Ingredients Paracetamol
Medicine Name CALPOL Six Plus 250mg/5ml Oral Suspension Active Ingredients Paracetamol
Medicine Name CALPOL SIX PLUS 250mg/5ml SUGAR/COLOUR FREE ORAL SUSPENSION Active Ingredients Paracetamol
Medicine Name CALPOL Six Plus Fastmelts 250 mg Paracetamol OrodispersibleTablets Active Ingredients Paracetamol
Medicine Name Daktarin 2% w/w Cream Active Ingredients Miconazole nitrate
Medicine Name Daktarin 2% w/w Cutaneous Powder Active Ingredients Miconazole nitrate
Medicine Name DAKTARIN 20mg/g Oral Gel Active Ingredients Miconazole
Medicine Name Imodium 2 mg Capsules Active Ingredients Loperamide Hydrochloride
Medicine Name Imodium Instants 2mg Orodispersible Tablets Active Ingredients Loperamide Hydrochloride
1 - 0 of 65 items.Total: Infinity pages

When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 21 October 2019 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text

Legal category: Supply through pharmacy only

Updated on 18 December 2018 PIL

Reasons for updating

  • Change to section 2 - interactions with other medicines, food or drink

Updated on 18 December 2018 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.9 - Overdose
  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 10 - Date of revision of the text

Legal category: Supply through pharmacy only

Updated on 26 June 2018 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)

Legal category: Supply through pharmacy only

Updated on 26 June 2018 PIL

Reasons for updating

  • Change to section 6 - marketing authorisation holder

Updated on 26 March 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Supply through pharmacy only

Updated on 26 March 2018 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Section 4.2 –  Updated with blue texts as per below as applicable


4.2      Posology and method of administration

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

Codeine-containing products should be used at the lowest effective dose for the shortest period of time.

Adults, children 16 years and over, and the elderly:  One to Ttwo Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one to two Migraleve Yellow tablets every 4-6 hours.

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

Paediatric population:

Children aged 16 – 18 years: One to two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one to two Migraleve Yellow tablets every 6 hours.

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.


Children 12 – 15 years:
 One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one Migraleve Yellow tablet every 46 hours.

Maximum dose:  4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.


Children aged below 12 years:

Do not give to children under 12 years of age because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see Section 4.3 and Section 4.4).

 

 

 

Section 4.9 –  Updated with blue texts as per below as applicable for Paracetamol with other remaining existing texts retained into full section.

Paracetamol

Paracetamol overdose can result in liver damage which may be fatal.

Symptoms generally appear within the first 24 hours and may comprise: nausea, vomiting, anorexia, pallor, and abdominal pain, or patients may be asymptomatic.

Overdose of paracetamol can cause liver cell necrosis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with increased prothrombin levels that may appear 12 to 48 hours after administration.

Liver damage is likely in patients who have taken more than the recommended amounts of paracetamol. It is considered that excess quantities of toxic metabolite become irreversibly bound to liver tissue.

Some patients may be at increased risk of liver damage from paracetamol toxicity:

Risk factors include;

•             Patients with liver disease

•             Elderly patients

•             Young children

•             Patients receiving long-term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

•             Patients who regularly consume ethanol in excess of recommended amounts

•             Patients with glutathione depletion  e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia

Acute renal failure with acute tubular necrosis may also develop.

Cardiac arrhythmias and pancreatitis have also been reported.

Emergency Procedure:

Immediate transfer to hospital.

Blood sampling to determine initial paracetamol plasma concentration. In the case of a single acute overdose, paracetamol plasma concentration should be measured 4 hours post ingestion.  Administration of activated charcoal should be considered if the overdose of paracetamol has been ingested within the previous hour.

The antidote N-acetylcysteine, should be administered as soon as possible in accordance with national treatment guidelines.

Symptomatic treatment should be implemented.

Please refer to local guidance for the treatment of paracetamol overdose.

Liver damage is possible in adults and adolescents (≥ 12 years of age) who have taken greater than 7.5 to 10g of paracetamol over a period of 8 hours or less. Fatalities are infrequent (less than 3-4% of untreated cases) and have rarely been reported with overdoses of less than 15g. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

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

Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

Regularly consumes ethanol in excess of recommended amounts.

Or

Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdose in the first 24 hours are pallor, hyperhidrosis, malaise, nausea, vomiting, anorexia and abdominal pain.  Liver damage may not become apparent until 48 to 72 hours after ingestion. This may include hepatomegaly, liver tenderness, jaundice, acute hepatic failure and hepatic necrosis.  Abnormalities of glucose metabolism and metabolic acidosis may occur. Blood bilirubin, hepatic enzymes, INR, prothrombin time, blood phosphate and blood lactate may be increased.  

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 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, 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) but results should not delay initiation of treatment with N-acetylcysteine beyond 8 hours after ingestion, as 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.

 

Section 10 – Date of Revision of the Text updated

 19 July 2017 14 March 2018

 

Updated on 23 March 2018 PIL

Reasons for updating

  • New PIL for new product

Updated on 23 March 2018 PIL

Reasons for updating

  • Change to section 3 - dose and frequency
  • Change to section 3 - use in children/adolescents
  • Change to section 3 - how to take/use
  • Change to section 3 - duration of treatment
  • Change to section 3 - overdose, missed or forgotten doses
  • Change to section 6 - date of revision

Updated on 9 August 2017 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 6.1 - List of excipients
  • Change to section 10 - Date of revision of the text

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

 

 

 

 

 

 

 

 

 

Section 4.2 – Sub heading ‘Adults, children 15 years and over, and the elderly’ replaced with ‘Adults, children 16 years and over, and the elderly’ and into paediatric population, subheading ‘Children 12-14 years’ is replaced with ‘Children 12-15 years’.

Deleted this text from section 4.2: “The use of this product in children aged less than 12 years of age is not recommended (see Section 4.3 and Section 4.4)”

Section 4.3 – Added text “Migraleve tablets are contraindicated for children below 12 years of age.”

Section 4.4 - Added text into section 4.4 under introductory paragraph - "They should also be advised to consult their doctor if symptoms persist. Migraleve tablets are intended for short-term use only."

Added text into section 4.4 under heading Codeine: "and/or high doses of codeine (see Section 4.8)."

Revised below sentence “Codeine should be used with caution in patients with convulsive disorders, head injuries, and in conditions in which intracranial pressure is raised by deleting text “at risk for additive CNS effects (see Section 4.5)” from above sentence.

Added text Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma and death (see Section 4.5)”

Replaced sentence “Use with caution in patients with renal and hepatic impairment” with Codeine should be used with caution in patients with renal and hepatic impairment.

Added text into section 4.4-

Opioids have also been associated with:

·         Serotonin syndrome resulting from concomitant administration of serotonergic drugs e.g., certain antidepressants, anti-anxiety, other psychiatric or migraine medications (see Section 4.5).

·         Adrenal insufficiency.

·         Androgen deficiency.

Under subheading “CYP2D6 metabolism” - Addedto into Population and Prevalence table under Northern European Prevalence i.e. 1% to 2 %

Replace “Use of the drug should be discontinued at the earliest sign of toxicity and medical help should be sought as soon as possible.” With Use of the drug should be discontinued and immediate medical advice

sought at the earliest sign of codeine toxicity including symptom such as confusion, shallow breathing or extreme sleepiness which may be life threatening.”

 

Deleted text into section 4.4 – Use of codeine is not recommended in children and adolescents between 12 and 18 years who have problems breathing.”

Section 4.5 – under subheading Codeinemay cuase additive CNS depression” replaced with may cause additive CNS depression and respiratory depression

Added new text under subheading Codeine –

“The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g. mirtazapine, trazodone, tramadol) and monoamine oxidase (MA) inhibitors may result in serotonin syndrome.”

Added new text under subheading Paracetamol –

“The use of drugs which induce hepatic microsomal enzymes, such as anticonvulsants and oral contraceptive steroids, may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentrations of the drug and a faster elimination rate.”

“Chronic alcohol intake may increase the hepatotoxicity of paracetamol overdose and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol. Acute alcohol intake may diminish an individual’s ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.”

Section 4.6 – under subheading Breastfeeding – text “Codeine should not be used during breastfeeding (see Section 4.3).” is replaced with “Codeine is contraindicated in breastfeeding women (see Section 4.3).”

Sentence “At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.” Slightly modified as “At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low concentrations and are unlikely to adversely affect the breast fed infant.”


Section 4.8 – Modified “Adverse reactions identified during clinical trials…..” with “Adverse drug reactions (ADR) identified during clinical trials…..”

SOC/Frequency/ADR table is modified as below:

Psychiatric disorders – “dependence” replaced withdrug dependence” with frequency not known.

Skin and subcutaneous tissue disorders – added ADR “Dermatitis” with frequency not known. Rashes2,3 is replaced with Rash3. Angioedema5,6 is replaced with Angioedema6.

Also added new text as per below into section 4.8 –

Other adverse reactions (codeine class effects) include:

·         Sedation

·         Vertigo

·         Bronchospasm

·         Gastrointestinal disorder, such as dyspepsia, nausea, vomiting, constipation

·         Euphoric mood

·         Drug dependence can develop following long-term use of high doses

 

Section 4.9 –  Sentence slightly corrected ‘Liver damage is possible in adults and adolescents (≥ 12 years of age)……’

 

Overdosage word replaced to overdose twice in section 4.9 as applicable.

 

Subheading Management” added as applicable.

Under subheading Codeine sentence “Other risks of codeine overdose include asthenia, cardiorespiratory arrest, cerebral oedema, coma, confusional state, convulsion, drug dependence, fatigue, hypoxia, ileus, renal failure, respiratory failure, stupor, and withdrawal symptoms.” is modified as per below:

“Other risks of codeine overdose include cardiorespiratory arrest, brain oedema, coma, confusional state, seizure, hypoxia, ileus, renal failure, respiratory failure and stupor.”

Section 5.1 –

Added text “Pharmacotherapeutic group: Opioids, codeine and other non-opioid analgesics ATC code: N02AJ09”

Section 6.1 – Typographical error corrected for spelling Colloidal Anhydrous Silica

Section 10: date of revision of text is updated with 19 July 2017. 

Updated on 9 August 2017 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 3 - use in children/adolescents
  • Change to section 4 - possible side effects
  • Change to section 6 - what the product contains
  • Change to section 6 - what the product looks like and pack contents
  • Change to section 6 - date of revision
  • Change to other sources of information section

Updated on 20 October 2015 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 4.9 - Overdose

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

PRESENT

PROPOSED

SPC

4.2       Posology and method of administration

 

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

 

Adults and the elderly:  Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, two Migraleve Yellow tablets every 4-6 hours.

 

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

 

Paediatric population:

 

Children 12 – 14 years:  One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one Migraleve Yellow tablet every 4 hours.

 

Maximum dose:  4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.

 

Children aged below 12 years:

Do not give to children under 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see section 4.3 Contra-indications and 4.4 Special Warnings and Precautions for Use)

 

4.2       Posology and method of administration

 

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

 

Adults, children 15 years and over, and the elderly:  Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, two Migraleve Yellow tablets every 4-6  hours.

 

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

 

Paediatric population:

 

Children 12 – 14 years:  One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one Migraleve Yellow tablet every 4 hours.

 

Maximum dose:  4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.

 

Children aged below 12 years:

Do not give to children under 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see sSection 4.3 Contra-indications and Section 4.4 Special Warnings and Precautions for Use).

 

The use of this product in children aged less than 12 years of age is not recommended (see Section 4.3 and Section 4.4)

 

4.3       Contraindications

 

Hypersensitivity to any of the ingredients.

 

In all paediatric patients (0-18 years of age) who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4 Special Warnings and Precautions for Use).

 

In women during breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation).

 

In patients for whom it’s known they are CY2D6 ultra-rapid metabolisers.

 

4.3       Contraindications

 

Hypersensitivity to any of the active substances (Paracetamol, Codeine phosphate and /or Buclizine hydrochloride) or to any of the excipients listed in section 6.1. ingredients.

 

Codeine-containing products are contraindicated for postoperative pain management Iin all paediatric patients (0-18 years of age) who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section Section 4.4 Special Warnings and Precautions for Use).

 

In women during breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation).

 

In patients for whom it’s known they are CY2D6 ultra-rapid metabolisers.

 

4.4       Special warnings and precautions for use

 

Migraine should be medically diagnosed.  Because some medicines do not combine, if you are already taking prescribed medicines please consult your doctor.  If symptoms persist consult your doctor.  Migraleve Pink tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor.  Do not exceed the stated dose.  May cause drowsiness.  Avoid alcoholic drink.  Should be used with caution in patients with severe renal disease or liver dysfunction.

 

Patients should be advised not to take other paracetamol-containing products concurrently.

 

Immediate medical advice should be sought in the event of an overdose even if the patient feels well because of the risk of irreversible liver damage.

 

Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

 

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

 

General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal.

Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

 

Population

Prevalence %

African/Ethiopian

29%

African American

3.4% to 6.5%

Asian

1.2% to 2%

Caucasian

3.6% to 6.5%

Greek

6.0%

Hungarian

1.9%

Northern European

1%-2%

 

Post-operative use in children

There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

 

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.

 

4.4       Special warnings and precautions for use

 

Migraine should be medically diagnosed.  Because some medicines do not combine, patients should be advised to tell their doctor if you they are already taking prescribed medicines please consult your doctorThey should also be advised to consult their doctor Iif symptoms persist. consult your doctor.  Migraleve Pink tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor. 

 

 

Do not exceed the stated dose.

 

Codeine

 

Codeine is an opioid agent. Tolerance, psychological and physical dependence may occur with prolonged use and/or high doses (see Section 4.8). Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

 

Codeine should be used with caution in patients at risk for additive CNS effects (see Section 4.5), convulsive disorders, head injuries, and in conditions in which intracranial pressure is raised.

 

Codeine should be used with caution in patients with decreased respiratory reserve, bronchial asthma, pulmonary oedema, obstructive airway disease, acute respiratory depression or obstructive bowel disorders and in patients at risk of paralytic ileus.

 

Use with caution in patients with renal and hepatic impairment.

 

Do not exceed the stated dose.  May cause drowsiness.  Avoid alcoholic drink.  Should be used with caution in patients with severe renal disease or liver dysfunction.

 

Patients should be advised not to take other paracetamol-containing products concurrently.

 

Immediate medical advice should be sought in the event of an overdose even if the patient feels well because of the risk of irreversible liver damage.

 

Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

 

CYP2D6 metabolism

 

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

 

Even at therapeutic dosage regimens, individuals who are ultra-rapid metabolisers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, cinfusion, or shallow breathing (see Section 4.9). other Ggeneral symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal.

Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

 

Population

Prevalence %

African/Ethiopian

29%

African American

3.4% to 6.5%

Asian

1.2% to 2%

Caucasian

3.6% to 6.5%

Greek

6.0%

Hungarian

1.9%

Northern European

1%-2%

 

When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and inform their patients about these risks and the signs of morphine overdose (see section 4.9).

 

Use of the drug should be discontinued at the earliest sign of toxicity and medical help should be sought as soon as possible.

 

Post-operative use in children

There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

 

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.

 

Use of codeine is not recommended in children and adolescents between 12 and 18 years who have problems breathing.

 

Paracetamol

 

Patients should be advised not to take other paracetamol-containing products concurrently.

 

Care is advised in the administration of paracetamol to patients with severe renal disease or liver dysfunction,

 

Chronic alcohol abusers should ask their doctors whether they should take paracetamol or other pain relievers or fever reducers.

 

Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

 

Buclizine

 

Buclizine should be used with caution in prostatic hypertrophy, urinary retention. Also where susceptibility to angle-closure glaucoma.

 

Buclizine is a sedating antihistamine that may enhance the sedative effects of central nervous system depressants, including alcohol, sedatives and tranquilizers. While taking this product, patients should be advised to avoid alcoholic beverages and consult a healthcare professional prior to taking with central nervous system depressants (see Section 4.5).

 

4.5       Interaction with other medicaments and other forms of interaction

 

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

 

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.

 

4.5       Interaction with other medicaments and other forms of interaction

 

Codeine

 

Concomitant use with central nervous system depressants (e.g. barbiturates, chloral hydrate, benzodiazepines, phenthiazines, alcohol and centrally acting muscle relaxants) may cuase additive CNS depression.

 

Concurrent use with other opioid receptor agonists may cause additive CNS depression, respiratory depression and hypotensive effect.

 

Codeine analgesia is believed to be dependent upon the cytochrome P450 isoenzyme CYP2D6 catalysed o-demethylation to form the active metabolite morphine although other mechanisms have been cited. An interaction with quinidine, methadone and paroxetine (CYP2D6 inhibitors) leading to decreased plasma concentrations of morphine has been described, which may have the potential to decrease codeine analgesia.

 

Paracetamol

 

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

 

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.

 

Buclizine

 

Sedating antihistamines, such as buclizine, have an additive effect with alocohol and other CNS depressants, Sedating antihistamines have an added antimuscarinic action with other antimuscarinic drugs such as atropine and some antidepressants (both tricyclic and MAOIs).

 

4.6       Fertility, pregnancy and lactation

 

Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose.  Whilst there are no specific reasons for contra-indicating Migraleve Pink during pregnancy, as with all drugs it is recommended that Migraleve Pink be used in pregnancy only when the physician has considered the need in respect of the patients’ welfare. 

 

Codeine should not be used during breastfeeding (see section 4.3 Contra-indications).

 

At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.

 

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine,  may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant which may be fatal.

 

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

4.6       Fertility, pregnancy and lactation

 

Pregnancy

 

This product should not be used during pregnancy unless the potential benefit of treatment to the mother outweighs the possible risks to the developing foetus.

 

Codeine crosses the placenta. Neonates who have been exposed to codeine in utero can develop withdrawal syndrome (neonatal abstinence syndrome) after delivery. Cerebral infarction has been reported in this setting.

 

When given to the mother in labelled doses, paracetamol crosses the placenta into foetal circulation as early as 30 minutes after ingestion and is effectively metabolised by foetal sulfate conjugation.

 

Clinical data with use of buclizine in humans are not adequate to establish safety during pregnancy. Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose.  Whilst there are no specific reasons for contra-indicating Migraleve Pink during pregnancy, as with all drugs it is recommended that Migraleve Pink be used in pregnancy only when the physician has considered the need in respect of the patients’ welfare. 

 

Breastfeeding

 

Codeine should not be used during breastfeeding (see sSection 4.3 Contra-indications).

 

At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.

 

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine,  may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant which may be fatal.

 

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

 

Paracetamol is excreted n breast milk in low concentrations (0.1% to 1.85% of the ingested maternal dose).

 

There are no data available relating to the safety of buclizine in breast-feeding mothers.

 

 

4.8       Undesirable effects

 

Rare allergic reactions to paracetamol, such as skin rashes, hives or itching.  Codeine may cause constipation. Buclizine hydrochloride may cause drowsiness.

 

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped.

 

Prolonged use of a painkiller for headaches can make them worse.

 

 

4.8       Undesirable effects

 

Rare allergic reactions to paracetamol, such as skin rashes, hives or itchingCodeine may cause constipation. Buclizine hydrochloride may cause drowsiness.

 

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped.

 

Prolonged use of a painkiller for headaches can make them worse.

 

Very rare cases of serious skin reactions have been reported with paracetamol

 

Adverse reactions identified during clinical trials and post-marketing experience with paracetamol, codeine, buclizine hydrochloride or the combinations of paracetamol/codeine or paracetamol/codeine/buclizine hydrochloride are listed below by System Organ Class (SOC).

 

The frequencies are defined as according to the following convention:

Very common (≥1/10);

Common (≥1/100 and <1/10);

Uncommon (≥1/1,000 and <1/100);

Rare (≥1/10,000 and <1/1,000); very rare (<1/10,000),

Not known frequency (cannot be estimated from the available data).

 

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence is unavailable, frequency category is listed as ‘Not known’.

 

System Organ Class (SOC)

Frequency

Adverse Drug Reaction (Preferred Term)

Blood and lymphatic system disorders

Not known

Blood disorder (including thrombocytopenia and agranulocytosis)4

Immune system disorders

Not known

Anaphylactic reaction3

 

Rare

Allergic reactions Hypersensitivity 2, 3,

 

Psychiatric disorders

Uncommon

Euphoric mood6

 

Not known

Agitation6

 

Not known

Addiction Dependence2

 

Not known

Drug withdrawal syndrome2

 

Nervous system disorders

Very common

Drowsiness Somnolence1,2,5

Common

Dizziness1, 6

 

Common

Headache6

 

Vascular disorders

Uncommon

Flushing6

Respiratory, thoracic and mediastinal disorders

Not known

Bronchospasm2

 

Not known

Dyspnoea6

 

Not known

Respiratory depression2

 

Gastrointestinal disorders

Very common

Nausea1,2

 

Common

Constipation1,2

 

Common

Dry mouth1

 

Common

Vomiting1,2

 

Uncommon

Abdominal pain6

 

Uncommon

Dyspepsia2

 

Hepatobiliary disorders

Not known

Liver injury3

Skin and subcutaneous tissue disorders

Common

Hyperhidrosis1

Rare Uncommon

Itching Pruritus2,6

 

Rare Uncommon

Skin Rashes2,3, 5

 

Rare Uncommon

Hives Urticaria2,3,5

 

Not known

Angioedema5,6

 

Renal and urinary disorders

Uncommon

Nephropathy toxic3

Investigations

Not known

Transaminases increased7

 

1 Adverse events reported by ≥1% of codeine/paracetamol treated subjects in 27 randomised placebo-controlled trials

2 Associated with codeine

3 Associated with paracetamol

4 Reported following paracetamol use, but not necessarily causally related to the drug

5 Associated with buclizine

6 Associated with paracetamol / codeine combination

7 Low level transaminase elevations may occur in some patients taking therapeutic doses of paracetamol; these elevations are not accompanied with liver failure and usually resolve with continued therapy or discontinuation of paracetamol.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail:medsafety@hpra.ie.

 

 

4.9       Overdose

 

Paracetamol

 

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

 

Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

Regularly consumes ethanol in excess of recommended amounts.

Or

Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

 

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.

 

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, 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) but results should not delay initiation of treatment beyond 8 hours after ingestion, as 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.

 

Codeine

 

The effects in codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

 

Codeine overdose associated with central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large.  The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

 

Management of codeine overdose includes general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable.  Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

 

Give naloxone if coma or respiratory depression is present.  Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient.  Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

 

4.9       Overdose

 

Paracetamol

 

Please refer to local guidance for the treatment of paracetamol overdose.

 

Liver damage is possible in adults and adolescents (≥ 12 years of age) who have taken greater than 7.5 to 10g or more of paracetamol over a period of 8 hours or less. Fatalities are infrequent (less than 3-4% of untreated cases) and have rarely been reported with overdoses of less than 15g. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

 

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

 

Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

Regularly consumes ethanol in excess of recommended amounts.

Or

Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

 

Symptoms

 

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, hyperhidrosis, malaise, vomiting, anorexia and abdominal pain.  Liver damage may not become apparent until 12 to 48 to 72  hours after ingestion.  This may include hepatomegaly, liver tenderness, jaundice, acute hepatic failure and hepatic necrosis. Abnormalities of glucose metabolism and metabolic acidosis may occur. Blood bilirubin, hepatic enzymes, INR, prothrombin time, blood phosphate and blood lactate may be increased.  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 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, 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) but results should not delay initiation of treatment with N-acetylcysteine beyond 8 hours after ingestion, as 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.

 

Codeine

 

The effects in codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

 

Codeine overdose associated with central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large.  The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely. Other risks of codeine overdose include asthenia, cardiorespiratory arrest, cerebral oedema, coma, confusional state, convulsion, drug dependence, fatigue, hypoxia, ileus, renal failure, respiratory failure, stupor, and withdrawal symptoms.

 

Management of codeine overdose includes general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable.  Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

 

Give naloxone if coma or respiratory depression is present.  Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient.  Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

 

Buclizine

 

Overdose with sedating antihistamines is associated with antimuscarinic, extrapyramidal, and CNS effects. When CNS stimulation predominates over CNS depression, which is more likely in children or the elderly, it causes ataxia, excitement, tremors, psychoses, hallucinations and convulsions; hyperpyrexia may also occur. Deepening coma and cardiorespiratory collapse may follow. In adults, CNS depression is more common with drowsiness, coma, and convulsions, progressing to respiratory failure and cardiovascular collapse.

 

Updated on 14 October 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to side-effects
  • Change to drug interactions
  • Change to further information section
  • Change to date of revision
  • Change to dosage and administration

Updated on 3 December 2013 SmPC

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Section 4.1

 

For the prevention and treatment of migraine attacks which can include the symptoms of migraine headache, nausea and vomiting. 

 

Route of administration:  oral.


TO:

 

For the prevention and treatment of migraine attacks which can include the symptoms of migraine headache, nausea and vomiting. 

 

Codeine is indicated in patients older than 12 years of age for the treatment of acute moderate pain which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen (alone).

 

Route of administration:  oral.


Section 4.2

 

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

 

Adults and the elderly:  Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, two Migraleve Yellow tablets every 4 hours.

 

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

 

Children 10 – 14 years:  One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one Migraleve Yellow tablet every 4 hours.

 

Maximum dose:  4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.

 

Do not give to children under 10 years of age except under medical supervision.


TO:

 

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.

 

Adults and the elderly:  Two Migraleve Pink tablets to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, two Migraleve Yellow tablets every 4 -6 hours.

 

Maximum dose:  8 tablets (two Migraleve Pink and six Migraleve Yellow) in 24 hours.

 

Paediatric population:

 

Children 12 – 14 years:  One Migraleve Pink tablet to be swallowed immediately it is known that a migraine attack has started or is imminent.  If further treatment is required, one Migraleve Yellow tablet every 4 hours.


Maximum dose:  4 tablets (one Migraleve Pink and three Migraleve Yellow) in 24 hours.

 

Children aged below 12 years:

Do not give to children under 12 years of age  because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see section 4.3 Contra-indications and 4.4 Special Warnings and Precautions for Use).


Section 4.3

 

Hypersensitivity to any of the ingredients.


TO:

 

Hypersensitivity to any of the ingredients.

 

In all paediatric patients (0-18 years of age) who undergo tonsillectomy and/or adenoidectomy for obstructive sleep apnoea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see section 4.4 Special Warnings and Precautions for Use).

 

In women during breastfeeding (see Section 4.6 Fertility, Pregnancy and Lactation).

 

In patients for whom it s known they are CY2D6 ultra-rapid metabolisers.


Section 4.4

 

Migraine should be medically diagnosed.  Because some medicines do not combine, if you are already taking prescribed medicines please consult your doctor.  If symptoms persist, consult your doctor.  Migraleve tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor.  Do not exceed the stated dose.  May cause drowsiness.  If affected, do not drive or operate machinery.  Avoid alcoholic drink.  Should be used with caution in patients with severe renal disease or liver dysfunction. Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

 

Patients should be advised not to take other paracetamol-containing products concurrently.

 

Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of irreversible liver damage.

 

Codeine is partially metabolised by CYP2D6. If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at low doses. General symptoms of opioid toxicity include nausea, vomiting, constipation, lack of appetite and somnolence. In severe cases this may include symptoms of circulatory and repiratory depression. Estimates indicate that up to 1 to 2% of the Caucasian population may be ultra-rapid metabolisers.

TO:

 

Migraine should be medically diagnosed.  Because some medicines do not combine, if you are already taking prescribed medicines please consult your doctor.  If symptoms persist, consult your doctor.  Migraleve tablets contain potent medicaments and should not be taken continuously for extended periods without the advice of a doctor.  Do not exceed the stated dose.  May cause drowsiness.  If affected, do not drive or operate machinery.  Avoid alcoholic drink.  Should be used with caution in patients with severe renal disease or liver dysfunction. Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

 

Patients should be advised not to take other paracetamol-containing products concurrently.

 

Immediate medical advice should be sought in the event of an overdose, even if the patient feels well, because of the risk of irreversible liver damage.

 

Codeine is metabolised by the liver enzyme CYP2D6 into morphine, its active metabolite. If a patient has a deficiency or is completely lacking this enzyme an adequate analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is an extensive or ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses. These patients convert codeine into morphine rapidly resulting in higher than expected serum morphine levels.

 

General symptoms of opioid toxicity include confusion, somnolence, shallow breathing, small pupils, nausea, vomiting, constipation and lack of appetite. In severe cases this may include symptoms of circulatory and respiratory depression, which may be life-threatening and very rarely fatal.

Estimates of prevalence of ultra-rapid metabolisers in different populations are summarized below:

 

Population

Prevalence %

African/Ethiopian

29%

African American

3.4% to 6.5%

Asian

1.2% to 2%

Caucasian

3.6% to 6.5%

Greek

6.0%

Hungarian

1.9%

Northern European

1%-2%

 

Post-operative use in children

There have been reports in the published literature that codeine given post-operatively in children after tonsillectomy and/or adenoidectomy for obstructive sleep apnoea, led to rare, but life-threatening adverse events including death (see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however there was evidence that these children were either ultra-rapid or extensive metabolisers in their ability to metabolise codeine to morphine.

 

Children with compromised respiratory function

Codeine is not recommended for use in children in whom respiratory function might be compromised including neuromuscular disorders, severe cardiac or respiratory conditions, upper respiratory or lung infections, multiple trauma or extensive surgical procedures. These factors may worsen symptoms of morphine toxicity.

Section 4.6

 

Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose.  Whilst there are no specific reasons for contra-indicating Migraleve during pregnancy, as with all drugs it is recommended that Migraleve be used in pregnancy only when the physician has considered the need in respect of the patients’ welfare. 

 

At normal therapeutic doses, codeine nd its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.

 

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of th active metabolite may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in th infant.

 

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

TO:

 

Although experiments in some animal species gave rise to adverse effects following the administration of buclizine to pregnant animals e.g. foetal abnormalities and maternal deaths, these occurred at doses in excess of 120 times the human daily dose.  Whilst there are no specific reasons for contra-indicating Migraleve during pregnancy, as with all drugs it is recommended that Migraleve be used in pregnancy only when the physician has considered the need in respect of the patients’ welfare. 

 

Codeine should not be used during breastfeeding (see section 4.3 Contra-indications).

 

At normal therapeutic doses, codeine and its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.

 

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine,  may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant which may be fatal.

 

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.

Section 5.1

 

Paracetamol has analgesic, antipyretic and mild, acute anti-inflammatory properties.  Paracetamol inhibits prostaglandin synthesis, especially in the CNS.  Paracetamol does not inhibit chronic inflammatory reactions.

 

Codeine is an opioid analgesic.  Codeine also has anti-tussive properties.

 

The combination of paracetamol and codeine has been shown to have hyperadditive analgesic effects in animals.

 

Buclizine is a piperazine derivative with the actions and uses of H1-receptor antagonists.  It has anti-muscarinic and central sedative properties.  It is used mainly for its anti-emetic properties.

TO:

 

Paracetamol has analgesic, antipyretic and mild, acute anti-inflammatory properties.  Paracetamol inhibits prostaglandin synthesis, especially in the CNS.  Paracetamol does not inhibit chronic inflammatory reactions.

 

Codeine is a centrally acting  weak analgesic. Codeine exerts its effect through μ opioid receptors, although codeine has low affinity for these receptors, and its analgesic effect is due to its conversion to morphine. Codeine, particularly in combination with other analgesics such as paracetamol, has been shown to be effective in acute nociceptive pain.

 

Codeine also has anti-tussive properties.

 

The combination of paracetamol and codeine has been shown to have hyperadditive analgesic effects in animals.

 

Buclizine is a piperazine derivative with the actions and uses of H1-receptor antagonists.  It has anti-muscarinic and central sedative properties.  It is used mainly for its anti-emetic properties.

Updated on 28 November 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to dosage and administration

Updated on 10 July 2013 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 28 June 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Prolonged regular use, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.



changed to:

Prolonged regular use for more than 3 days, except under medical supervision, may lead to physical and psychological dependence (addiction) and result in withdrawal symptoms, such as restlessness and irritability once the drug is stopped.

Updated on 31 May 2011 PIL

Reasons for updating

  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change due to user-testing of patient information

Updated on 20 May 2011 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Section 4.2:
Addition of:

Do not take for more than 3 days continuously without medical review. If prescribed do not take for longer than directed.



Section 4.4:
Addition of:

Codeine is partially metabolised by CYP2D6. If a patient has a deficiency or is completely lacking this enzyme they will not obtain adequate analgesic effects. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. Howver, if the patient is an ultra-rapid metaboliser there is an increased risk of developing side effects of opioid toxicity even at low doses. General symptoms of opioid toxicity include nausea, vomiting, constipation, lack of appetite and somnolence. In severe cases this may include symptoms of circulatory and repiratory depression. Estimates indicate that up to 1 to 2% of the Caucasian population may be ultra-rapid metabolisers. 

Section 4.5:
Addition of:

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

 

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.



Section 4.6:
Text on breastfeeding changed to:

At normal therapeutic doses, codeine nd its active metabolites may be present in breast milk at very low doses and are unlikely to adversely affect the breast fed infant.

 

However if the patient is an ultra rapid metaboliser of CYP2D6, higher levels of teh active metabolite may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in teh infant.

 

If symptoms of opioid toxicity develop in either the mother or the infant, then all codeine containing medicines should be stopped and alternative non-opioid analgesics prescribed. In severe cases consideration should be given to prescribing naloxone to reverse these effects.   


Section 4.8:
Addtion of:

Regular prolonged use of codeine is known to lead to addiction and symptoms of restlessness and irritability may result when treatment is stopped.

 

Prolonged use of a painkiller for headaches can make them worse.


Section 4.9:
Information on overdose changed to:

Paracetamol

 

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

 

Is on long term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s Wort or other drugs that induce liver enzymes.

Or

Regularly consumes ethanol in excess of recommended amounts.

Or

Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

 

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.

 

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, 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) but results should not delay initiation of treatment beyond 8 hours after ingestion, as 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.

 

Codeine

 

The effects in codeine overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

 

Codeine overdose associated with central nervous system depression, including respiratory depression, may develop but is unlikely to be severe unless other sedative agents have been co-ingested, including alcohol, or the overdose is very large.  The pupils may be pin-point in size; nausea and vomiting are common. Hypotension and tachycardia are possible but unlikely.

 

Management of codeine overdose includes general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable.  Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg.

Give naloxone if coma or respiratory depression is present.  Naloxone is a competitive antagonist and has a short half-life so large and repeated doses may be required in a seriously poisoned patient.  Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

 

Updated on 11 October 2010 PIL

Reasons for updating

  • Change of manufacturer

Updated on 18 August 2009 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 22 May 2009 SmPC

Reasons for updating

  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text
  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.6 - Pregnancy and lactation

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company



Section 1

Full name is now:

Migraleve Pink Film-coated Tablets

Paracetamol 500mg

Codeine phosphate 8mg

Buclizine hydrochloride 6.25mg



Section 2

The following statement added:

For a full list of excipients, see section 6.1.

Section 3

(Tablets) added to end of description of pharmaceutical form.

Section 4.6

Statement "Migraleve Pink is not contraindicated in breastfeeding mothers" has been removed.

Section 6.5

Statement "Not all packs sizes may be marketed" added

Section 10

Changed to November 2008

Updated on 11 February 2009 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Inclusion of actives during renewal.

Updated on 25 August 2008 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Change in MAH from Pfizer Consumer Healthcare, Pottery Road, Dun Laoghaire to McNeil Healthcare Ireland Limited, Airton Road, Tallaght, Dublin 24.

Updated on 28 August 2007 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition

Legal category: Supply through pharmacy only

Free text change information supplied by the pharmaceutical company

Section 1: Full name added. Migraleve Pink Film coated Tablets
Section 2: Re-written to give more clarity. No change to composition.

Updated on 6 January 2006 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Supply through pharmacy only