Gen-Payne 10 Mg/200 Mg/250 Mg Capsules

GEN-PAYNE CAPSULES are indicated for the relief of mild to moderate pain of 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.
Adults and children over 12 years
One to two capsules four to six hourly and not more than six capsules per twenty-four hours. Consult your doctor if no relief is obtained with the recommended dosage.
Paediatric population
GEN-PAYNE CAPSULES are not recommended for children under twelve years of age.
Method of administration
GEN-PAYNE CAPSULES are administered orally. The capsules must be swallowed with water and not chewed.

• Impaired hepatic and renal function.
• Heart failure.
• History of gastrointestinal perforation, ulceration or bleeding (PUBs) related to previous NSAIDs, including GEN-PAYNE CAPSULES.
• Active or history of recurrent ulcer/haemorrhage/perforations.
• Cardiovascular disease.
• Hypersensitivity to any of the active ingredients.
• Contraindicated in respiratory depression, especially in the presence of cyanosis and excessive bronchial secretion, after operations on the biliary tract, acute alcoholism, convulsive disorders, head injuries and conditions in which intracranial pressure is raised. It should not be given during an attack of bronchial asthma or in heart failure secondary to chronic lung disease.
• Contra-indicated in patients taking monoamine oxidase inhibitors or within fourteen days of stopping such treatment.
• GEN-PAYNE CAPSULES are contraindicated in patients with a history of hypersensitivity reactions to aspirin or other NSAIDu2019s, including those in whom attacks of asthma, angioedema, urticaria, or rhinitis have been precipitated by aspirin or any other NSAID.
• 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 (see sections 4.4 and 4.6).

The safety of continuous administration of GEN-PAYNE CAPSULES has not been established for a period greater than four weeks.
Codeine phosphate
Exceeding the prescribed dose, together with prolonged and continuous use of this medication, may lead to dependency and addiction.
Codeine phosphate should be given with caution to patients with hypothyroidism, adrenocortical insufficiency, asthma, impaired liver or kidney function, prostatic hyperplasia, shock, hypotension, inflammatory or obstructive bowel disorders or myasthenia gravis.
The dosage should be reduced in elderly and debilitated patients.
Ibuprofen
Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with GEN-PAYNE CAPSULES therapy. In view of GEN-PAYNE CAPSULESu2019 inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.
The elderly have an increased frequency of adverse reactions to NSAIDs including GEN-PAYNE CAPSULES, especially gastrointestinal perforation, ulceration and bleeding (PUBs) which may be fatal.
The risk of gastrointestinal perforation, ulceration or bleeding (PUBs) is higher with increasing doses of GEN-PAYNE CAPSULES, in patients with a history of ulcers, and the elderly.
When gastrointestinal bleeding or ulceration occurs in patients receiving GEN-PAYNE CAPSULES, treatment with GEN-PAYNE CAPSULES should be stopped.
GEN-PAYNE CAPSULES 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.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. GEN-PAYNE CAPSULES should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as GEN-PAYNE CAPSULES. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophillia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue GEN-PAYNE CAPSULES and evaluate the patient immediately.
Use of NSAIDs including GEN-PAYNE CAPSULES during the third trimester of pregnancy, may result in persistent pulmonary hypertension of the newborn. The onset of labour may be delayed and its duration increased (see section 4.6).
GEN-PAYNE CAPSULES should be used with caution in patients with infection since symptoms such as fever and inflammation may be masked.
Other precautions to be observed include administration to patients with haemorrhagic disorders, asthma, a history of hypersensitivity reactions to aspirin or other nonsteroidal anti-inflammatory medications and impaired renal, hepatic or cardiac function. Should be used with caution in the elderly.
Caution is advised in those patients who are receiving coumarin anticoagulants (see section 4.5).
Foetal Toxicity: Limit use of NSAIDs, including GEN-PAYNE CAPSULES, between 20 to 30 weeks of pregnancy due to the risk of oligohydramnios/foetal renal dysfunction. Avoid use of NSAIDs in women at 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.

Codeine phosphate
The depressant effects of codeine are enhanced by depressants of the central nervous system such as alcohol, anaesthetics, hypnotics and sedatives, and phenothiazines.
Ibuprofen
Lithium, methotrexate and cardiac glycosides: increased plasma concentrations may result.
ACE inhibitors, cyclosporin, tacrolimus, or diuretics: concurrent administration may increase the risk of nephrotoxicity.
Effects on renal function may lead to reduced excretion of some medicines.
Antihypertensives: the antihypertensive effects of some antihypertensives, including ACE inhibitors, beta blockers, and diuretics may be reduced. There may also be an increased risk of hyperkalaemia with ACE inhibitors and potassium-sparing diuretics.
Quinolones: convulsions may occur.
Moclobemide: the effects of NSAIDu2019s might be enhanced.
Phenytoin and sulphonylurea antidiabetics: effects may be enhanced.
Mifepristone: it is advised that NSAIDu2019s should be avoided 8 to 12 hours after mifepristone use, because of a theoretical risk that these prostaglandin synthetase inhibitors may alter the efficacy of mifepristone.
Zidovudine: may increase the risk of haemotoxicity.
NSAIDs: use of two or more NSAIDs concomitantly could result in an increase in side effects.
Alcohol, bisphosphonates or oxpentifylline: possible increased risk of NSAID associated gastrointestinal bleeding and ulceration.
Corticosteroids: increased risk of gastrointestinal perforation, ulceration or bleeding (PUBs).
Anti-coagulants: GEN-PAYNE CAPSULES may enhance the effects of anti-coagulants such as warfarin.
Anti-platelet medicines and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.

GEN-PAYNE CAPSULES are not recommended for use by pregnant or breastfeeding women (see section 4.3). Use of non-steroidal anti-inflammatory drugs during the third trimester of pregnancy, may result in persistent pulmonary hypertension of the new-born. Use of NSAIDs, including GEN-PAYNE CAPSULES, 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 GEN-PAYNE CAPSULES 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 (see sections 4.3 and 4.4). The onset of labour may be delayed and its duration increased.
Fertility
No data on male and female fertility are available.

Patients should be advised not to drive or operate machinery if affected by dizziness or sedation. This medicine can impair cognitive function and can affect a patient's ability to drive safely. Patients should be advised that they do not engage in the above activities until they are aware of the measure to which GEN-PAYNE CAPSULES affects them.

a. Summary of the safety profile
The most commonly observed adverse events are gastrointestinal in nature.
b. Tabulated summary of adverse reactions
Codeine phosphate
SYSTEM ORGAN CLASS
FREQUENCY
ADVERSE REACTIONS
Psychiatric disorders
Frequency unknown
Changes of mood, hallucinations.
Nervous system disorders
Frequency unknown
Drowsiness, dizziness, headache, confusion, restlessness, vertigo, raised intracranial pressure.
Eye disorders
Frequency unknown
Miosis.
Cardiac disorders
Frequency unknown
Bradycardia, tachycardia, palpitations.
Vascular disorders
Frequency unknown
Orthostatic hypotension.
Gastrointestinal disorders
Frequency unknown
Nausea, vomiting, constipation, dry mouth.
Skin and subcutaneous tissue disorders
Frequency unknown
Sweating and facial flushing. Reactions such as urticaria, and pruritus.
Renal and urinary disorders
Frequency unknown
Micturition may be difficult and there may be ureteric or biliary spasm.
Reproductive system and breast disorders
Frequency unknown
Decreased libido or potency.
General disorders and administrative site conditions
Frequency unknown
Hypothermia.
Ibuprofen
SYSTEM ORGAN CLASS
FREQUENCY
ADVERSE REACTIONS
Blood and the lymphatic system disorders
Less frequent
Anaemias, thrombocytopenia, neutropenia, eosinophilia, agranulocytosis. Frequency unknown
Reversible inhibition of platelet aggregation.
Immune system disorders (Hypersensitivity reactions include)
Frequent
Rashes. Less frequent
Angioedema, bronchospasm, hepatotoxicity and aseptic meningitis. Frequency unknown
Fever.
Nervous system disorders
Frequent
Dizziness. Less frequent
Nervousness, depression, drowsiness, insomnia. Frequency unknown
Headache, vertigo.
Eye disorders
Less frequent
Visual disturbances.
Ear and labyrinth disorders
Less frequent
Tinnitus.
Cardiac disorders
Less frequent
Oedema, hypertension, cardiac failure. Frequent
Nausea and abdominal pain.
Gastrointestinal disorders
Less frequent
Vomiting, diarrhoea, flatulence, constipation, dyspepsia, peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, melaena, haematemesis, ulcerative stomatitis, gastritis. Frequency unknown
Exacerbation of colitis and Crohnu2019s disease, gastrointestinal discomfort.
Skin and subcutaneous tissue disorders
Less frequent
Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) (see section 4.4).
Renal and urinary disorders
Less frequent
Renal failure. Frequency unknown
Interstitial nephritis, nephrotic syndrome.
Paracetamol
SYSTEM ORGAN CLASS
FREQUENCY
ADVERSE REACTIONS
Blood and the lymphatic system disorders
Less frequent
Haematological reactions including thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis.
Immune system disorders
Less frequent
Hypersensitivity reactions.
Gastrointestinal disorders
Frequency unknown
Pancreatitis.
Skin and subcutaneous tissue disorders
Less frequent
Skin rashes. The rash is usually erythematous or urticarial but sometimes more serious and accompanied by fever and mucosal lesions.
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. Health care 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 directly to a hospital. A delay in starting treatment may mean that antidote is given too late to be effective. Evidence of liver damage is often delayed until after the time for effective treatment has lapsed. Susceptibility to paracetamol toxicity is increased in patients who have taken repeated high doses (greater than 5 u2013 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 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. Liver damage may become apparent 12 to 48 hours, or later 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. 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.
Treatment for paracetamol overdosage
Although evidence is limited it is recommended that any adult person who has ingested 5 - 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 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.
N-acetylcysteine should be administered to all cases of suspected overdose as soon as possible preferably within eight 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. An initial dose of 150 mg/kg N-acetylcysteine in 200 ml dextrose injection given intravenously over 15 minutes, followed by an infusion of 50 mg/kg in 500 ml dextrose injection over the next four hours, and then 100 mg/kg in 1 000 ml dextrose injection over the next sixteen hours. The volume of intravenous fluid should be modified for children. 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 four hours for seventeen doses. A plasma paracetamol level should be determined four hours after ingestion in all cases of suspected overdosage. Levels done before four hours may be misleading. Patients at risk of liver damage, and hence requiring continued treatment with N-acetylcysteine, can be identified according to their 4-hour plasma paracetamol level. The plasma paracetamol level can be plotted against time since ingestion in the nomogram below. The nomogram should be used only in relation to a single acute ingestion. A semi-logarithmic plot of plasma-paracetamol concentration against hours after ingestion. (Reference: Martindale). 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. Monitor all patients with significant ingestions for at least ninety-six hours.
Codeine phosphate
Symptoms of overdosage include excitement and, in children, convulsions may occur. Large doses produce respiratory depression. Treatment of overdosage is symptomatic and supportive.
Ibuprofen
The most likely symptoms of overdosage are nausea, vomiting and tinnitus. Treatment is symptomatic and supportive.