Myprodol Capsules 10 mg/200 mg/250 mg. Hard capsules.

MYPRODOL 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
One to two capsules four hourly and not more than twelve capsules per twenty-four hours. Consult your doctor if no relief is obtained with the recommended dosage.
Paediatric population
Not recommended for children under twelve years of age.

Method of administration
MYPRODOL is administered orally. The capsules must be swallowed with water and not chewed.

• Heart failure,
• Impaired hepatic and renal function,
• Peptic ulceration,
• History of gastrointestinal perforation, ulceration or bleeding (PUBs) related to previous NSAIDs, including MYPRODOL CAPSULES,
• 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, 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,
• Contraindicated in patients taking monoamine oxidase inhibitors or within fourteen days of stopping such treatment,
• Caution is advised in those patients who are receiving coumarin anticoagulants,
• Patients who are sensitive to aspirin should not be given MYPRODOL CAPSULES,
• 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.

The safety of continuous administration of MYPRODOL 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.
Paracetamol: This product contains paracetamol which may be fatal in overdose. In the event of overdosage 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 in excess of those recommended may cause severe liver damage.
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 MYPRODOL CAPSULE therapy,
• In view of MYPRODOL CAPSULEu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients,
• Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs including MYPRODOL 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 MYPRODOL CAPSULES, in patients with a history of ulcers, and the elderly,
• When gastrointestinal bleeding or ulceration occurs in patients receiving MYPRODOL CAPSULES treatment with MYPRODOL CAPSULES should be stopped,
• MYPRODOL 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. MYPRODOL 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 MYPRODOL. 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 MYPRODOL and evaluate the patient immediately.
• Foetal Toxicity: Limit use of NSAIDs, including MYPRODOL CAPSULES, between 20 and 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.
• Between 20 weeks and 30 weeks gestation, limit MYPRODOL CAPSULES use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if MYPRODOL CAPSULES treatment extends beyond 48 hours. Discontinue MYPRODOL CAPSULES if oligohydramnios occurs and follow up according to clinical practice.
• Severe cutaneous adverse reactions (SCARs): Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines. If a patient develops SCAR, treatment with MYPRODOL CAPSULES must immediately be discontinued and appropriate treatment instituted (see Section 4.8).

• NSAID: Use of two or more NSAIDs concomitantly could result in an increase in side effects.
• Corticosteroids: increased risk of gastrointestinal perforation, ulceration or bleeding (PUBs)
• Anti-coagulants: MYPRODOL 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.

MYPRODOL CAPSULES are not recommended for use by pregnant or breastfeeding women. 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 MYPRODOL 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 MYPRODOL 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 MYPRODOL CAPSULES affects them.

a. Summary of the safety profile
In view of the productu2019s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients. The most commonly observed adverse events are gastro-intestinal in nature.
b. Tabulated summary of adverse reactions
Ibuprofen:

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.
Ibuprofen
The most likely symptoms of overdosage are epigastric pain and nausea.
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.