Numark Max Strength Sinus Relief With Decongestant Capsules
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Wockhardt Max Strength Cold & Flu Capsules Health Essentials Max Strength Cold & Flu Relief Capsules Numark Max Strength Cold & Flu with decongestant Capsules Numark Max Strength Sinus relief with decongestant Capsules
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Phenylephrine hydrochloride 6mg
For excipients see 6.1
3 PHARMACEUTICAL FORM
Capsules
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the relief of nasal congestion and congestion of mucous membranes of the upper respiratory tract associated with the common cold, and relief of cold and influenza, including relief of aches and pains, sore throat, headache, fatigue and drowsiness, and lowering of temperature.
4.2 Posology and method of administration
For oral administration. Swallow whole with water. Do not chew.
Adults and children over 12 years of age:
1-2 capsules every 4-6 hours. Maximum of 8 capsules in any 24 hour period.
Children under 12 years of age:
Do not give to children under 12 years.
The dose should not be repeated more frequently than every 4 hours.
Do not take for more than 3 days without consulting a doctor.
4.3 Contraindications
Hypersensitivity to paracetamol, phenylephrine or to any of the excipients.
Caffeine:
Hypersensitivity to caffeine.
Do not give to patients with a history of peptic ulceration.
Phenylephrine hydrochloride
• Hyper susceptible patients
• Hyperthyroidism
• Aneurysm
• Arteriosclerosis
• Phaeochromocytoma
• Cardiovascular disease including hypertension
• Prostatic enlargement
• Diabetes mellitus
• Closed angle glaucoma
• Concomitant use of other sympathomimetic decongestants
• Beta-blockers - (see section 4.5)
• Monoamine oxidase inhibitors (MAOIs), including moclobemide (or within 14 days of stopping treatment, see section 4.5)
4.4 Special warnings and precautions for use
Paracetamol
Care is advised in the administration of paracetamol to patients with renal or hepatic impairment. The hazards of overdose are greater in those with alcoholic liver disease. Paracetamol should be given with care to patients with alcoholic dependence.
Paracetamol is well tolerated by the majority of people with asthma. However, a small percentage of aspirin sensitive asthmatics are also sensitive to paracetamol. The likelihood of a reaction to paracetamol increases with a patient’s level of sensitivity to aspirin (see also 4.8 Undesirable Effects).
Caution should be exercised when using paracetamol prior to (less than 72 hours) or concurrently with intravenous busulfan (see section 4.5 Interactions).
Caffeine
Care is advised in the administration of caffeine to patients with cardiac disease.
Excessive intake of caffeine (e.g. coffee, tea and some canned drinks) should be avoided while taking this product.
Phenylephrine
• Care is advised in the administration of phenylephrine in patients with cardiovascular conditions such as hypertension, occlusive vascular disease, Prinzmetal’s angina, thromboembolic disorders, following myocardial infarction or a history of ischaemic heart disease.
• Phenylephrine should be used with caution in elderly patients.
• If any of the following occur, Maximum Flu Strength Cold Control Capsules should be stopped
• Hallucinations
• Restlessness
• Sleep disturbances
The following warnings appear in the leaflet and on the label:
Label-
Contains paracetamol.
Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.
Do not take anything else containing paracetamol while taking this medicine. Talk to a doctor at once if you take too much of this medicine, even if you feel well.
Leaflet-
Talk to a doctor at once if you take too much of this medicine even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.
General points:
• Do not exceed the recommended dose.
• If symptoms persist consult a doctor.
• Do not give to children under 12 years.
• Keep out of the reach and sight of children.
• Do not take for more than three days unless your doctor agrees.
Patients should be advised not to take other paracetamol-containing products concurrently.
4.5 Interaction with other medicinal products and other forms of interaction Paracetamol
Alcohol: Paracetamol should be given with care to patients with alcohol dependence (see Section 4.4).
Analgesics: Diflunisal increases blood concentrations of paracetamol.
Anion-exchange resins: Absorption reduced by colestyramine; administration should be separated by at least one hour.
Antibacterials: Isoniazid may increase the risk of hepatotoxicity with therapeutic doses of paracetamol.
Anticoagulants: 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.
Antiepileptics: Carbamazepine, phenobarbital, phenytoin and primidone can reduce the effects of paracetamol and increase the risk of hepatotoxicity.
Cytotoxic drugs: Paracetamol possibly inhibits metabolism of intravenous busulfan (manufacturer of intravenous busulfan advises caution within 72 hours of paracetamol).
Motility stimulants: The speed of absorption of paracetamol may be increased by metoclopramide or domperidone
Oral Contraceptives: Paracetamol is cleared from the body more quickly in women taking oral contraceptives and the analgesic effects may be reduced.
Uricosurics: Probenecid can reduce the loss of paracetamol from the body.
Caffeine
Antibacterials: Some quinolone antibiotics, including enoxacin, pipemidic acid and ciprofloxacin can reduce the clearance of caffeine and prolong its plasma half-life.
Antidepressants: Fluvoxamine can reduce the clearance of caffeine and increase its stimulant and side effects.
Antiepileptics: Phenytoin may increase the clearance of caffeine. Antipsychotics: Caffeine may increase serum clozapine levels. Benzodiazepines: Caffeine can reduce the sedative effects of diazepam. Disulfiram: may reduce the clearance of caffeine.
Diuretics: Concomitant use of xanthines with diuretics may increase the risk of hypokalaemia.
Ephedrine/ephedra alkaloids in dietary supplements (Ma Huang):
Concomitant use may raise blood pressure; hypertension, tachycardia, subarachnoid haemorrhage, cardiac arrest and neurosis have been reported.
Lithium: Caffeine may increase the clearance of lithium.
Mexiletine: may reduce the clearance of caffeine.
Oestrogens and progestogens: Oral contraceptives or oestrogen replacement therapy may reduce the clearance of caffeine.
Phenylpropanolamine: Concomitant administration may increase blood pressure, resulting in hypertensive crises in a few susceptible individuals. Manic psychosis has occurred. Phenylpropanolamine can increase serum caffeine levels.
Theophylline: concomitant administration can increase plasma theophylline and plasma caffeine levels.
Phenylephrine Hydrochloride
Anaesthetics, general: Concomitant administration of phenylephrine with general anaesthetics (e.g. halothane, cyclopropane) may potentiate arrhythmias.
Anticholinergic drugs: Maximum Flu Strength Cold Control Capsules enhance the effects of anticholinergic drugs (such as TCAs).
There is an increased risk of hypertension when used with atropine.
Antidepressants: Maximum Flu Strength Cold Control Capsules should not be given to patients treated with monoamine oxidase inhibitors (MAOIs) and/or RIMAs (such as moclobemide), or within 14 days of stopping treatment with MAOIs: increased risk of hypertensive crisis (see Section 4.3 Contraindications).
There is an increased risk of hypertension when used with tricyclic antidepressants e.g. imipramine.
Antihypertensives (including adrenergic neurone blockers and beta-blockers): Maximum Flu Strength Cold Control Capsules may block the hypotensive effect. Adrenergic neurone blockers may enhance the hypertensive effect of phenylephrine.
Cardiac glycosides: increased risk of dysrhythmias.
Appetite suppressants and amphetamine-like psychostimulants: risk of hypertension.
Antimigraine drugs: Ergot alkaloids (ergotamine and methysergide):-increased the risk of ergotism, including vasoconstriction and hypertension.
Oxytocics: there is a potential increased risk of hypertension with oxytocin.
Sympathomimetics: concomitant use with other sympathomimetics can increase the hypertensive effect.
4.6 Pregnancy and lactation Paracetamol
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.
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast-feeding.
Caffeine
Taken during pregnancy, it appears that the half-life of caffeine is prolonged. This is a possible contributing factor in hypermesis gravidarum. Caffeine crosses the placenta, and foetal blood and tissue levels similar to maternal concentrations are achieved. Cardiac dysrhythmias have been noted in the foetuses and neonates of mothers consuming varying levels of caffeine during pregnancy. Decreased birth weight may be associated with maternal caffeine intake and cigarette smoking. Limited evidence suggests that high maternal caffeine intake may be associated with fetotoxicity including spontaneous abortion, however, other factors may have contributed to the findings. Decreased fertility may be associated with maternal caffeine intake. Caffeine intake during pregnancy should be kept to a minimum.
Caffeine is excreted in breast milk, but with moderate intake amounts are probably too low to be clinically significant. Regular intake of large amounts of caffeine by nursing mothers can affect the infant, including irritability and poor sleeping patterns.
Phenylephrine hydrochloride:
The safety of phenylephrine during pregnancy has not been established but there is some evidence suggesting a possible association of foetal abnormalities with first trimester exposure to phenylephrine. As an alpha-adrenoceptor stimulant, phenylephrine might provoke uterine changes, which can result in foetal asphyxia and/or foetal bradycardia. There is no information on the excretion of phenylephrine into breast milk; however no clinical problems have been documented.
In view of the above, Maximum Flu Strength Cold Control Capsules should be avoided during pregnancy and lactation unless prescribed by a doctor.
4.7 Effects on ability to drive and use machines
Paracetamol
None
Caffeine
None
Phenylephrine Hydrochloride
May cause dizziness, if affected, do not drive or operate machinery.
4.8 Undesirable effects Paracetamol:
Adverse effects of paracetamol are rare.
Haematological: There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol. Leucopenia, neutropenia and pancytopenia have been reported in association with paracetamol.
Immune system: Hypersensitivity including skin rash, urticaria or angioedema may occur. A small percentage of aspirin-sensitive asthmatics are also sensitive to paracetamol. In such cases, the deterioration in respiratory function induced by paracetamol is milder and shorter than with aspirin (see also 4.4 Special warnings and precautions for use).
Renal and urinary disorders: Nephropathy has been associated with chronic high dose use.
Skin and subcutaneous tissue disorders: Very rare cases of serious skin reactions have been reported.
Caffeine:
Cardiac disorders: Cardiac arrhythmias including tachycardia and extrasystoles.
Gastrointestinal disorders: Nausea, vomiting, increased gastric secretions and gastro-oesophageal reflux.
General disorders: Irritability
Nervous system disorders: Tremor may be experienced.
Psychiatric disorders: Restlessness, excitement, anxiety and insomnia may be experienced.
Renal and urinary disorders: Diuresis.
Phenylephrine Hydrochloride:
Cardiovascular effects:
• Tachycardia/palpitations
• Other cardiac dysrhythmias
• Hypertension with headache
• Reflex bradycardia
Metabolic disorders:
Metabolic acidosis
Muscle and tissue disorders:
Weakness
CNS effects:
• Irritability
• Anxiety
• Restlessness
• Excitability
• Insomnia
• Hallucinations and paranoid delusions Skin reactions including rash:
Hypersensitivity reactions - including that cross-sensitivity may occur with other sympathomimetics. Piloerection.
Vascular disorders:
Vasoconstriction
Other reactions:
• Nausea and /or vomiting
• Headache
• Dizziness
• Tremor
• Difficulty in micturition and urinary retention 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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, phenobarbital, 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 overdose in the first 24 hours are sweating, 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, hypotension, cerebral oedema, coma and death. Prothrombin time may increase with deteriorating liver function. 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 arrythmias and pancreatitis have been reported.
Treatment
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines, 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 eight hours post ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours from ingestion should be discussed with the NPIS or a liver unit.
Caffeine
Symptoms: Large doses may cause restlessness, excitement, psychosis, muscle tremor, tinnitus, hyperglycaemia, hypokalaemia, diuresis, dehydration, tachycardia and extrasystoles. Emesis and convulsions may occur.
Treatment
No specific antidote. Elimination may be enhanced by repeated oral doses of activated charcoal. Symptomatic and supportive treatment.
Hypokalemia should be corrected by intravenous infusion of potassium chloride.
Intravenous diazepam or barbiturates may be used to control convulsions. Phenylephrine Hydrochloride
Severe hypertension and cerebral haemorrhage are possible. If overdose is suspected, consult your doctor immediately.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Paracetamol
Paracetamol has analgesic and antipyretic properties. Analgesic effects are thought to be related to inhibition of prostaglandin synthesis. An antipyretic effect has been demonstrated where fever exists but normal body temperature is not lowered. The drug acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. The failure of paracetamol to exert anti-inflammatory activity may be attributed to the fact that it is only a weak inhibitor of cyclo-oxygenase in the presence of the high concentrations of peroxides that are found in inflammatory lesions. Further, paracetamol does not inhibit neutrophil activation, as do other NSAIDs.
Single or repeated therapeutic doses of paracetamol have no effect on the cardiovascular and respiratory systems, nor does the drug produce gastric irritation, erosion, or bleeding.
Caffeine
The primary effect of caffeine is central nervous system stimulation, mainly on the higher centres. This expressed in terms of increased vigilance, wakefulness, relief from fatigue, increased mental activity, improved performance and improved mood. Other effects include diuresis and increased cardiac output with peripheral vasodilation. Caffeine, a methylxanthine, exerts its pharmacological effects by increasing calcium permeability in the sarcoplasmic reticulum, inhibiting phosphodiesterase and promoting accumulation of cyclic AMP. Caffeine is also a competitive, non-selective antagonist at adenosine A1 and A2A receptors. Evidence suggests that adenosine receptor antagonism is the most important factor responsible for most pharmacological effects of methylxanthines in doses that are administered therapeutically.
Phenylephrine
Phenylephrine is a relatively selective ^-adrenoceptor agonist. It has weak a2-adrenoceptor agonist activity, some activity as a low cardioselective P-adrenoceptor agonist and minimal central stimulant activity. It is also termed a sympathomimetic vasoconstrictor. Most of the a1-stimulant activity is due to an indirect effect via release of noradrenaline. Sympathomimetic vasoconstriction forms the basis of its decongestant actions, for which it is most widely used.
5.2 Pharmacokinetic properties Paracetamol
Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract, with peak plasma concentrations reached in 10-15 minutes after oral dosing. Dissolution and gastric emptying are rate-limiting steps; the mean half-time of absorption from upper small intestine is within minutes. The absolute oral bioavailability is about 80% and is independent of dose in the range 5 to 20mg/kg. Oral bioavailability of paracetamol is subject to first pass metabolism. Paracetamol is rapidly and uniformly distributed into most body tissues. About 25% of paracetamol in blood is bound to plasma proteins. The mean plasma paracetamol half-life following a therapeutic dose is about 2.3 hours in healthy adults, with a range of 1.5-3 hours. Paracetamol crosses the placenta and is present in breast milk.
After therapeutic doses, 90 - 100% of the drug may be recovered in the urine within the first day, primarily after hepatic conjugation with glucuronic acid (about 60%), sulphuric acid (about 35%) or cysteine (about 3%); small amounts of hydroxylated and deacetylated metabolites have also been detected. A small proportion of paracetamol undergoes P450-mediated N-hydroxylation to form N-acetyl-benzoquinoneimine, a highly reactive intermediate. After large doses of paracetamol, this metabolite is formed in amounts sufficient to deplete hepatic glutathione. Under these circumstances, reaction with sulphydryl groups in hepatic proteins is increased and hepatic necrosis can result. Renal clearance is about 10ml/min.
Phenylephrine
Phenylephrine is absorbed after oral administration but is subject to extensive presystemic metabolism, much of which occurs in the enterocytes. As a consequence, systemic bioavailability is only about 40%. Following administration, peak plasma concentrations are achieved in 1-2 h. The mean plasma half-life is in the range 2-3 h. Penetration into the brain appears to be minimal.
Phenylephrine undergoes extensive biotransformation in the liver. Both phenylephrine and its metabolites are excreted in urine, with less than 20% as unchanged drug. The principal routes of metabolism are to sulphate conjugates, formed largely in the gut wall, and deamination by monoamine oxidase. There are no data on the extent of protein binding. Excretion in breast milk appears to be minimal.
Caffeine
Caffeine is absorbed readily after oral administration to the extent of 99%, peak plasma levels occur in 15-45 min. The half-life of caffeine in plasma shows considerable variation with the reported values ranging from 3.0-7.5 hours. It is widely and rapidly distributed throughout the body, and passes readily into the central nervous system and saliva. Approximately 17% of the drug is bound to plasma proteins. Caffeine crosses the placenta and has been shown to distribute into milk in a milk-to-serum concentration of 0.52.
In adults, caffeine is metabolised almost completely in the liver via oxidation, demethyl ati on, and acetylation, and is excreted in the urine as 1-methyluric acid, 1-methylxanthine and other metabolites with only about 1% unchanged. Neonates have a greatly reduced capacity to metabolise caffeine and it is largely excreted unchanged in the urine until hepatic metabolism becomes significantly developed.
5.3 Preclinical safety data
The active ingredients have been in widespread use for many years and have a well-established therapeutic profile. There is no further data of relevance to the prescriber in addition to that presented in the other sections of the SmPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Pregelatinised starch Sodium lauryl sulphate Croscarmellose sodium Magnesium stearate Talc
Purified water
Empty hard gelatin capsule shell (E-171, E-127, E-104 and E-131)
6.2 Incompatibilities
None
6.3 Shelf life
2 years from the date of manufacture
6.4 Special precautions for storage
Do not store above 25°C
6.5 Nature and contents of container
Capsules are packaged in blister strips
Blister strips consist of a 35gsm paper/9p soft tempered aluminium foil lid and 250p PVDC film base in cartons.
Pack sizes: 12, 16 (GSL)
6.6 Special precautions for disposal
No special instructions
7 MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd Ash Road North Wrexham LL13 9UF UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 29831/0172
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
20/06/2003 / 23/02/2011
10 DATE OF REVISION OF THE TEXT
03/08/2016