Nocomypro 400 mg/ 325 mg Tablet

NOCOMYPRO is indicated for the relief of mild to moderate pain of inflammatory origin or non-inflammatory origin with or without fever.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE. Use the lowest effective dose for the shortest possible duration of treatment. Not recommended for children under twelve years. Adults and children over 12 years: 2 tablets every 4 hours when necessary. Do not exceed 6 tablets in 24 hours. Tablets are to be taken with food or after meals with sufficient water. If taking NOCOMYPRO of pain and the pain persists for longer than 7 days, or if taking NOCOMYPRO for fever and the fever persists for longer than 3 days or if the condition deteriorates or new symptoms develop, a re-evaluation of the condition is required by the doctor.
Paediatric population
The safety and efficacy of NOCOMYPRO in children under 12 years of age have not yet been established.
Method of administration
For oral administration.

• Hypersensitivity to ibuprofen, paracetamol or to any of the excipients listed in section 6.1.
• Avoid use of NSAIDs in women around 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/foetal renal dysfunction and premature closure of the foetal ductus arteriosus.
• NOCOMYPRO is contraindicated in heart failure.
• History of gastrointestinal perforation, ulceration, or bleeding (PUBs) related to previous NSAIDs, including NOCOMYPRO.
• Active or history of recurrent ulcer/haemorrhage/perforations.
• Patients sensitive to aspirin or another non-steroidal anti-inflammatory medicine.
• Uncontrolled asthma or bronchospasm.
• Nasal polyps associated with aspirin-induced bronchospasm.
• Patients with bleeding disorders.
• Severe liver impairment.
• Renal impairment.
• Pregnancy and lactation.
• Patients who are receiving coumarin-anticoagulants.

This product contains paracetamol which may be fatal in overdose or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Centre must be contacted immediately. Dosages of paracetamol in excess of those recommended may cause severe liver damage. NOCOMYPRO should be used with caution in the following conditions:
u2022 Alcoholism or impaired liver function - Increased risk of hepatotoxicity.
u2022 Renal function impairment - Increased risk of adverse effects with prolonged use of high doses, occasional use is acceptable.
The antipyretic, analgesic and anti-inflammatory action of ibuprofen may mask symptoms of the occurrence or worsening of infection.
NOCOMYPRO should be used with caution in the following:
u2022 In patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NOCOMYPRO therapy. In view of NOCOMYPROu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.
u2022 In patients with significant risk factors for cardiovascular events (e.g., hypertension, hyperlipidaemia, diabetes mellitus, smoking) and should only be treated with diclofenac after careful consideration.
u2022 Inflammatory or ulcerative disease of the upper or lower gastrointestinal tract.
u2022 Asthma - May be exacerbated.
u2022 Allergic conditions - Possibility of cross sensitivity.
u2022 Anaemia - May be exacerbated.
u2022 Bleeding disorders - Increased risk of hepatotoxicity.
u2022 Renal function impairment - Renal failure may be provoked, especially in patients with pre-existing renal impairment. Avoid alcohol: Increased risk of liver toxicity, especially in alcoholics with high doses and prolonged use.
Diabetic patients: May experience false results with blood glucose tests.
Elderly patients: The elderly has an increased frequency of adverse reactions to NSAIDs including NOCOMYPRO, especially hepatic or renal effects and gastrointestinal perforation, ulceration, and bleeding (PUBs) which may be fatal.
Gastrointestinal:
u2022 The risk of gastrointestinal perforation, ulceration, or bleeding (PUBs) is higher with increasing doses of NOCOMYPRO in patients with a history of ulcers, and the elderly.
u2022 When gastrointestinal bleeding or ulceration occurs in patients receiving NOCOMYPRO treatment with NOCOMYPRO should be stopped.
u2022 NOCOMYPRO should be given with caution to patients with a history of gastrointestinal disease (e.g., ulcerative colitis, Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the condition may be exacerbated.
Skin reactions: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. NOCOMYPRO should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Surgery: Possible enhanced bleeding if surgery is required.
Foetal Toxicity: Regular use of NSAIDs such as NOCOMYPRO during the third trimester of pregnancy, may result in premature closure of the foetal ductus arteriosus in utero, and possibly, in persistent pulmonary hypertension of the new-born. The onset of labour may be delayed, and its duration increased. Limit use of NSAIDs, including NOCOMYPRO, between 20 to 30 weeks of pregnancy due to the risk of oligohydramnios/foetal renal dysfunction. Avoid use of NSAIDs in women around 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/foetal renal dysfunction and premature closure of the foetal ductus arteriosus.
If NSAID treatment is necessary between 20 weeks and 30 weeks gestation, limit NOCOMYPRO use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NOCOMYPRO treatment extends beyond 48 hours. Discontinue NOCOMYPRO if oligohydramnios occurs and follow up according to clinical practice.

• Hepatotoxic medicines: Increased risk of hepatotoxicity.
• Enzyme inducing medicines: Increased risk of hepatotoxicity. Possible decrease in therapeutic effects of paracetamol.
• Metoclopramide: Absorption of paracetamol may be accelerated.
• Cholestyramine: Absorption of paracetamol is reduced if given within one hour of cholestyramine.
• Anticoagulants: NOCOMYPRO may enhance the effects of anti-coagulants such as warfarin and the possibility of gastrointestinal bleeding.
• Alcohol, corticosteroids, clopidogrel, ticlopidine, bisphosphonates, pentoxifylline: Increased risk of gastrointestinal bleeding and ulceration.
• Antidiabetic agents: Hypoglycaemic effects of these medicines may be increased.
• Digoxin: Increase in serum digoxin concentrations.
• Lithium: Increase in the steady-state concentration of lithium.
• Methotrexate: Increased and prolonged methotrexate plasma concentration and increased risk of methotrexate toxicity.
• Nephrotic medicines e.g., ciclosporin: Increased risk of nephrotoxicity.
• Antihypertensives or diuretics: Reduction or reversal of the antihypertensive effect may occur.
• Bone marrow depressants: The leucopenic and/or thrombocytopenic effects of these medicines may be increased.
• Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (PUBs).
• Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
• NSAIDs: use of two or more NSAIDs concomitantly could result in an increase in side effects.

Pregnancy
Safety and efficacy in pregnancy have not been established. Use of NSAIDs, including NOCOMYPRO, can cause premature closure of the foetal ductus arteriosus and foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, the use of NOCOMYPRO dose and duration between 20 and 30 weeks of gestation should be limited and avoided at around 30 weeks of gestation and later in pregnancy.
Breastfeeding
Safety and efficacy in lactation have not been established.
Fertility
No information available.

No information available. Refer to section 4.8.

a. Summary of the safety profile
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohnu2019s disease, gastritis.
b. Tabulated summary of adverse reactions
A tabulated summary of undesirable effects has been included for ibuprofen and paracetamol (in combination) below. Adverse reactions are listed by system organ class.
SYSTEM ORGAN CLASS
FREQUENCY
ADVERSE REACTIONS
Blood and lymphatic system disorders
Less frequent
Agranulocytosis, thrombocytopaenia, anaemia, neutropenia, eosinophilia.
Nervous system disorders
Frequent
Dizziness.
Less frequent
Nervousness, headache, tinnitus, depression, drowsiness, insomnia.
Eye disorders
Less frequent
Blurred vision, changes in visual colour perception and other toxic amblyopia.
Cardiac disorders
Less frequent
Tachycardia, flushing, increase in blood pressure/ hypertension, heart failure.
Gastrointestinal Disorders
Frequent
Nausea, abdominal pain, vomiting, diarrhoea, flatulence, constipation, dyspepsia, peptic ulceration, perforation, or gastrointestinal bleeding, melena, haematemesis gastritis.
Frequency unknown
Ulcerative stomatitis, exacerbation of colitis and Crohnu2019s disease.
Hepatobiliary disorders
Less frequent
Hepatitis.
Skin and subcutaneous tissue disorders
Frequency unknown
Allergic dermatitis, erythema multiforme, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Renal and urinary disorders
Less frequent
Oedema, impairment of renal function, acute reversible renal impairment.
Frequency unknown
Interstitial nephritis and nephritic syndrome.
General disorders and administration site conditions
Less frequent
Hypersensitivity reactions (fever, rashes, hepatotoxicity, and aseptic meningitis).
Post marketing experience
No information available.
c. Description of selected adverse reactions
No information available.
d. Paediatric population
The safety and efficacy of NOCOMYPRO in children under 12 years of age have not yet been established (see section 4.2).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Paracetamol:
Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person to the nearest hospital directly. A delay in starting treatment may mean that the antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for the effective treatment has lapsed. Specialised treatment is essential as soon as possible.
Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 to 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of medicines that induce liver microsomal oxidation such as barbiturates, isoniazid, rifampicin, phenytoin and carbamazepine.
Symptoms of paracetamol overdose
u2022 Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, vomiting, anorexia, and possibly, abdominal pain. Mild symptoms during the first two days of acute poisoning do not reflect the potential seriousness of the overdosage.
u2022 Liver damage may become apparent 12 to 48 hours later, or after ingestion initially by elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration and prolongation of the prothrombin time. Liver damage may lead to encephalopathy, coma, and death.
u2022 Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Abnormalities of glucose metabolism and metabolic acidosis may occur. Cardiac arrhythmias have been reported. Nausea, vomiting, anorexia, and abdominal pain may persist for a week or more. Cerebral oedema and nonspecific myocardial depression have also occurred.
Treatment of paracetamol overdosage:
u2022 Although evidence is limited, it is recommended that any adult person who has ingested 5 to 10 grams or more of paracetamol (or a child who has had more than 140 mg/kg) within the preceding four hours, should have the stomach emptied by gastric lavage (emesis may be adequate for children) and a single dose of 50 g activated charcoal given via the lavage tube. Ingestion of amounts of paracetamol smaller than this may require treatment in patients susceptible to paracetamol poisoning (see above). In patients who are stuperose or comatose endotracheal intubation should precede gastric lavage in order to avoid aspiration.
u2022 Specialised therapy with an antidote such as acetylcysteine or methionine may be necessary. If decided upon, acetylcysteine should be administered IV as soon as possible.
u2022 N-Acetylcysteine: N-Acetylcysteine should be administered to all cases of suspected overdose as soon as possible, preferably within 8 hours of overdosage, although treatment up to 36 hours after ingestion may still be of benefit, especially if more than 150 mg/kg of paracetamol was taken.
u2022 IV: An initial dose of 150 mg/kg in 200 mL dextrose injection, given intravenously over 15 minutes, followed by an intravenous infusion of 50 mg/kg in 500 mL of dextrose injection over the next 4 hours and then 1 000 mL dextrose injection over the next 16 hours. The volume of intravenous fluids should be modified for children.
u2022 Orally: Although the oral formulation is not the treatment of choice, 140 mg/kg dissolved in water may be administered initially, followed by 70 mg/kg every 4 hours for 17 doses.
u2022 If activated charcoal is used, then it should be removed by gastric lavage as it may interfere with the absorption of orally administered acetylcysteine and decrease the efficacy.
u2022 A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours, unless high, may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine can be identified according to their plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the normogram below. The nomogram should be used only in relation to a single acute ingestion.
u2022 Those whose plasma paracetamol levels are above the u201cnormal treatment lineu201d, should continue N-acetylcysteine treatment with 100 mg/kg IV over sixteen hours repeatedly until recovery. Patients with increased susceptibility to liver damage as identified above, should continue treatment if concentrations are above the u201chigh risk treatment lineu201d. Prothrombin index correlates best with survival.
u2022 Monitor all patients with significant ingestions for at least ninety-six hours.
Ibuprofen
Symptoms of ibuprofen overdosage:
u2022 Gastrointestinal symptoms (e.g., abdominal pain, nausea, vomiting), central nervous system symptoms (e.g., lethargy, drowsiness), gastrointestinal haemorrhage, acute renal failure, convulsions and coma (see section 4.8).