SYNDOL

Active substance: PARACETAMOL

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Syndol Caplets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Paracetamol BP 450.00mg
Codeine Phosphate BP 10.00mg
Doxylamine Succinate NF 5.00mg
Caffeine BP 30.00mg
Also contains E110 (sunset yellow), E104 (quinoline yellow) and lactose
monohydrate
For full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Tablets

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the short term treatment of acute moderate pain which is not relieved by
paracetamol, ibuprofen or aspirin alone such as headache, tension headache,
migraine, neuralgia, toothache, dysmenorrhoea, muscular and rheumatic aches
and pains and post-operative analgesia following surgical or dental
procedures.

4.2

Posology and method of administration
Route of administration: Oral
Adults and Children over 12 years:
One or two tablets every four to six hours as needed for relief. Total dosage
over a 24 hour period should not normally exceed eight tablets.
Do not take for more than 3 days continuously without medical review.
Codeine should be used with caution in the elderly and debilitated patients as
they may be more susceptible to the respiratory depressant effects.

4.3

Contraindications
Hypersensitivity to paracetamol, codeine or other opioid analgesics, or any of
the other constituents.

Due to interaction with the doxylamine succinate component, the concomitant
use of Syndol with monoamine inhibitors (MAOIs) or within 14 days of
stopping treatment with these medicines is contraindicated, as there is a risk of
serotonin syndrome. (See section 4.5).

4.4

Special warnings and precautions for use
Do not exceed the stated dose.
Do not take concurrently with any other paracetamol or codeine containing
compounds.
This product may cause drowsiness.
Keep out of the reach and sight of children.
Care is advised in the administration of this preparation to patients with
impaired kidney or liver function and in those with hypertension,
hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy, urinary
retention, susceptibility to angle-closure glaucoma, shock, obstructive bowel
disorders, acute abdominal conditions (e.g. peptic ulcer), recent
gastrointestinal surgery, gallstones, myasthenia gravis, a history of cardiac
arrhythmias or convulsions, and in patients with a history of drug abuse or
emotional instability.
Codeine may induce faecal impaction, producing incontinence, spurious
diarrhoea, abdominal pain and rarely colonic obstruction. Elderly patients may
metabolise or eliminate opioid analgesics more slowly than younger adults.
Administration of pethidine and possibly other opioid analgesics to patients
taking a monoamine oxidase inhibitor (MAOI) has been associated with very
severe and sometimes fatal reactions. See also Section 4.3 regarding
contraindication of taking Syndol with MAOIs because of the doxylamine
component.
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 respiratory depression. Estimates indicate that up to 1 to 2%
of the Caucasian population may be ultra-rapid metabolisers.
The hazards of overdose are greater in those with non-cirrhotic alcoholic liver
diseases.
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency or glucose-galactose malabsorption should not take this
medicine.
E110 (sunset yellow) and E104 (quinoline yellow) may cause allergic
reactions.
The label will state:
Front of Pack:
• Can cause addiction



For three days use only
Back of Pack:
• For the short term treatment of acute moderate pain where other pain killers
have not worked. Do not take less than four hours after taking other pain
killers. For tension headaches, migraines, muscular pains and tension.
• If you need to take this medicine continuously for more than three days you
should see your doctor or pharmacist.
• This medicine contains codeine which can cause addiction if you take it
continuously for more than three days. If you take this medicine for
headaches for more than three days it can make them worse.
The leaflet will state:
Headlines section (to be prominently displayed):
• This medicine can only be used for the short term treatment of acute
moderate pain where other pain killers have not worked.
• You should only take this product for a maximum of three days at a time. If
you need to take it for longer than three days you should see your doctor or
pharmacist for advice.
• This medicine contains codeine which can cause addiction if you take it
continuously for more than three days. This can give you withdrawal
symptoms from the medicine when you stop taking it.
• If you take this medicine for headaches for more than three days it can
make them worse.
Section 1: What the medicine is for
• Syndol is used for the short term treatment of acute moderate pain which is
not relieved by paracetamol, ibuprofen and aspirin alone such as headache,
including muscle contraction or tension headache, migraine, neuralgia,
period pain, toothache and other dental pain, muscular and rheumatic aches
and pains and for pain relief following surgery or dental procedures.
Section 2: Before taking
• This medicine contains codeine which can cause addiction if you take it
continuously for more than three days. This can give you withdrawal
symptoms from the medicine when you stop taking it.
• If you take a painkiller for headaches for more than three days it can make
them worse.
• (In the “Pregnancy and breast-feeding” subsection) Usually it is safe to take
Syndol while breast feeding as the levels of the active ingredients of this
medicine in breast milk are too low to cause your baby any problems.
However, some women who are at increased risk of developing side effects
at any dose may have higher levels in their breast milk. If any of the
following side effects develop in you or your baby, stop taking this
medicine and seek immediate medical advice; feeling sick, vomiting,
constipation, decreased or lack of appetite, feeling tired or sleeping for
longer than normal, and shallow or slow breathing.
Section 3: Dosage
• Do not take for more than 3 days. If you need to use this medicine for more
than three days you must speak to your doctor or pharmacist.



This medicine contains codeine and can cause addiction if you take it
continuously for more than three days. When you stop taking it you may get
withdrawal symptoms. You should talk to your doctor or pharmacist if you
think you are suffering from withdrawal symptoms.

Section 4: Side effects
• Some people may have side-effects when taking this medicine. If you have
any unwanted side-effects you should seek advice from your doctor,
pharmacist or other healthcare professional. Also you can help to make sure
that medicines remain as safe as possible by reporting any unwanted sideeffects via the internet at www.mhra.gov.uk/yellowcard; alternatively you
can call Freephone 0808 100 3352 (available between 10am-2pm Monday –
Friday) or fill in a paper form available from your local pharmacy.
How do I know if I am addicted?
If you take the medicine according to the instructions on the pack it is unlikely
that you will become addicted to the medicine. However, if the following
apply to you it is important that you talk to your doctor:
• You need to take the medicine for longer periods of time.
• You need to take more than the recommended dose.
• When you stop taking the medicine you feel very unwell but you feel better
if you start taking the medicine again.

4.5

Interaction with other medicinal products 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 daily use of paracetamol with increased risk of bleeding;
occasional doses have no significant effect.
Syndol may enhance the sedative effects of CNS depressants such as alcohol,
barbiturates, anaesthetics, hypnotics, other opioid analgesics, anxiolytic
sedatives, antipsychotics, tricyclic antidepressants and phenothiazines,
resulting in increased CNS depression. It may also have an additive
antimuscarinic action with other drugs, such as atropine and some
antidepressants.
The hypotensive actions of diuretics and anti hypertensive agents may be
potentiated when used concurrently with opioid analgesics. Concurrent use of
hydroxyzine with codeine may result in increased analgesia as well as
increased CNS depressant and hypotensive effects.
The respiratory depressant effect caused by neuromuscular blocking agents
may be additive to the central respiratory depressant effects of opioid
analgesics. Quinidine can inhibit the analgesic effect of codeine.
Concurrent use of codeine with antidiarrhoeal and antiperistaltic agents such
as loperamide and kaolin may increase the risk of severe constipation.
Concomitant use of antimuscarinics or medications with antimuscarinic action
may result in an increased risk of severe constipation which may lead to
paralytic ileus and/or urinary retention.

Codeine may delay the absorption of mexiletine and thus reduce the
antiarrhythmic effect of the latter. Codeine may antagonise the gastrointestinal
effects of metoclopramide, cisapride and domperidone. Cimetidine inhibits the
metabolism of opioid analgesics resulting in increased plasma concentrations.
Naxolone antagonise the analgesic, CNS and respiratory depressant effects of
opioid analgesics. Naltrexone also block the therapeutic effect of opioids.
Doxylamine: Monamine oxidase inhibitors (MAOIs) or within 14 days of
stopping treatment with these products as there is a risk of serotonin syndrome
(see Section 4.3).
Concomitant administration of pethidine and possibly other opioid analgesics
to patients taking MAOIs has been associated with very severe and sometimes
fatal reactions such as severe CNS excitation or depression, including
hypertension or hypotension. Although this has not been documented with
codeine, it is possible that a similar interaction may occur and therefore the
use of codeine should be avoided while the patient is taking MAOIs and for 2
weeks after MAOI discontinuation.
Incompatibilities: Codeine has been reported to be incompatible with
phenobarbitone sodium forming a codeine-phenobarbitone complex, and with
potassium-iodide, forming crystals of codeine periodide. Acetylation of
codeine phosphate by aspirin has occurred in solid dosage forms containing
the two drugs, even at low moisture levels.
Interference with laboratory tests: Opioid analgesics interfere with a number of
laboratory tests including plasma amylase, lipase, bilirubin, alkaline
phosphatase, lactate dehydrogenase, alanine aminotransferase and aspartate
aminotransferase. Opioids may also interfere with gastric emptying studies as
they delay gastric emptying and with hepatobiliary imaging using technetium
Tc 99m disofenin as opioid treatment may cause constriction of the sphincter
of Oddi and increase biliary tract pressure.

4.6

Fertility, pregnancy and lactation
Epidemiological studies in human pregnancy have shown no ill effects due to
paracetamol used in the recommended dosage, but patients should follow the
advice of their doctor regarding its use.
Codeine crosses the placenta. There is no adequate evidence of safety in
human pregnancy and a possible association with respiratory and cardiac
malformations has been reported. Regular use during pregnancy may cause
physical dependence in the foetus leading to withdrawal symptoms in the
neonate. Use during pregnancy should be avoided if possible.
Use of opioid analgesia during labour may cause respiratory depression in the
neonate, especially the premature neonate. These agents should not be given
during the delivery of a premature baby.
At normal therapeutic doses codeine and its active metabolites may be present
in breast milk at very low doses and is unlikely to adversely affect the breast
fed infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6,
higher levels of the active metabolites may be present in breast milk and on
very rare occasions may result in symptoms of opioid toxicity in the infant.

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

4.7

Effects on ability to drive and use machines
Some side effects related to doxylamine succinate include drowsiness (usually
diminishes within a few days), paradoxical stimulation, headaches,
psychomotor impairment, hypotension, dizziness, confusion, tremor and
convulsions.
Opioid analgesics can impair mental function and cause blurred vision and
dizziness. Rare side effects may include convulsions, hallucinations, blurred or
double vision, dizziness and orthostatic hypotension
These side effects may have a noticeable impact on the ability to driving and
operate machinery. Patients should ensure they are not affected before driving
or operating machinery.
See section 4.8 for more information on side effects.

4.8

Undesirable effects
Doxylamine succinate:
Common side effects:
CNS effects: Drowsiness (usually diminishes within a few days), paradoxical
stimulation, headaches, psychomotor impairment.
Antimuscarinic effects: Urinary retention, dry mouth, blurred vision,
gastrointestinal disturbances, thickened respiratory tract secretions
Rare side effects: Hypotension, extrapyramidal effects, dizziness, confusion,
depression, sleep disturbances, tremor, convulsions, palpitation, arrhythmia
hypersensitivity reactions, blood disorders and liver dysfunction.
Adverse effects of paracetamol are rare but hypersensitivity including skin
rash may occur. There have been a few reports of blood disorders including
thrombocytopenia and agranulocytosis but these were not necessarily causally
related to paracetamol.
The most frequent undesirable effects of codeine are constipation and
drowsiness. Less frequent effects are nausea, vomiting, sweating, facial
flushing, dry mouth, blurred or double vision, dizziness, orthostatic
hypotension, malaise, tiredness, headache, anorexia, vertigo, bradycardia,
palpitations, respiratory depression, dyspnoea, allergic reactions (itch, skin
rash, facial oedema) and difficulties in micturition (dysuria, increased
frequency, decrease in amount). Side effects, which occur rarely, include
convulsions, hallucinations, nightmares, uncontrolled muscle movements,
muscle rigidity, mental depression and stomach cramps.
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.

4.9

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
a, Is on long term treatment with carbamazepine, phenobarbitone, phenytoin,
primidone, rifampicin, St John’s Wort or other drugs that induce liver
enzymes.
Or
b, Regularly consumes ethanol in excess of recommended amounts.
Or
c, Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV
infection, starvation, cachexia.
Symptoms
Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea,
vomiting, anorexia and abdominal pain. Liver damage may become apparent
12 to 48 hours after ingestion. Abnormalities of glucose metabolism and
metabolic acidosis may occur. In severe poisoning, hepatic failure may
progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema,
and death. Acute renal failure with acute tubular necrosis, strongly suggested
by loin pain, haematuria and proteinuria, may develop even in the absence of
severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.
Management
Immediate treatment is essential in the management of paracetamol 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). Treatment with N-acetylcysteine may be used up to 24 hours after
ingestion of paracetamol, however, the maximum protective effect is obtained
up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply
after this time. If required the patient should be given intravenous Nacetylcysteine, in line with the established dosage schedule. If vomiting is not
a problem, oral methionine may be a suitable alternative for remote areas,
outside hospital. Management of patients who present with serious hepatic
dysfunction beyond 24h from ingestion should be discussed with the NPIS or
a liver unit.
Codeine
The effects in overdosage will be potentiated by simultaneous ingestion of
alcohol and psychotropic drugs.

Symptoms
Central nervous system depression, including respiratory depression, may
develop but is unlikely to be severe unless other sedative agents have been coingested, 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
This should include 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 350mg
or a child more than 5mg/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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Paracetamol - analgesic, antipyretic
Codeine Phosphate - analgesic
Doxylamine Succinate - antihistamine
Caffeine - mild stimulant

5.2

Pharmacokinetic properties
The pharmacokinetics of paracetamol, codeine phosphate and caffeine are
widely published (see Goodman and Gilman's Pharmacological Basis of
Therapeutics, Seventh Edition pgs. 693, 505 and 596 respectively.
Doxylamine succinate is readily absorbed from the gastrointestinal tract.
Following oral administration the effects start within 15 to 30 minutes and
peak within one hour. In humans 60 - 80% of doxylamine given has been
recovered in urine at 24 hours post-dose.

5.3

Preclinical safety data
None stated

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Povidone
Croscarmellose Sodium
Corn Starch
Magnesium Stearate

Talc
Purified Water
Opadry II Yellow (lactose monohydrate, titanium dioxide, hypromellose,
quinoline yellow (E104), sunset yellow (E110) and polyethylene glycol 4000)

6.2

Incompatibilities
Not applicable

6.3

Shelf life
36 months, unopened

6.4

Special precautions for storage
None stated

6.5

Nature and contents of container
Blister strips: 250 micron PVC and aluminium foil 20 micron coated with a 15
micron PVC layer
Blister strips are presented in cardboard cartons. Pack sizes are 4*, 10, 20, 30
tablets (*sample pack)

6.6

Special precautions for disposal
Not applicable

7

MARKETING AUTHORISATION HOLDER
SSL International plc
103 – 105 Bath Road
Slough
Berkshire
SL1 3UH

8

MARKETING AUTHORISATION NUMBER(S)
PL 17905/0077

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
27/02/2009

10

DATE OF REVISION OF THE TEXT
9/8/2012

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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