Source: Health Products Regulatory Authority (ZA) Revision Year: 2023 Publisher: PHARMACARE LIMITED, Healthcare Park, Woodlands Drive, Woodmead, 2191
TRIPARC is contraindicated in:
TRIPARC contains paracetamol which may be fatal in overdose. In the event of overdosage and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or Poison Control Centre must be contacted immediately.
DO NOT EXCEED THE RECOMMENDED DAILY DOSE.
Dosages in excess of those recommended may cause severe liver damage.
Do not use continuously for more than 10 days without consulting your doctor. Medical advice should be sought if cough persists, or if it is accompanied by high fever, skin rash or persistent headache.
The use of NSAIDs around 20 weeks gestation or later in pregnancy may cause rare but serious foetal renal dysfunction leading to oligohydramnios and, in some cases constriction of the ductus arteriosus (see section 4.6).
Aspirin, as in TRIPARC, should be administered with caution to patients with impaired renal or hepatic function, dyspepsia, anaemia and when the patient is dehydrated, or suffering from diabetes mellitus. Prolonged use of high doses may lead to anaemia, blood dyscrasias, gastrointestinal haemorrhage, peptic ulceration, renal papillary necrosis and in the presence of uncontrolled hypertension.
There is an association between aspirin, as in TRIPARC, and Reye’s syndrome when given to children and teenagers during or immediately after a viral illness (such as chickenpox and influenza). Reye’s syndrome is a rare disease which affects the brain and liver and can be fatal. For this reason, children and teenagers (between 12 and 16 years of age) who have or are recovering from chicken pox or flu-like symptoms should not use this medicine, unless prescribed by a healthcare practitioner (see section 4.3). When using this medicine, if changes in behaviour with nausea and vomiting occur, the patient should consult a doctor because these symptoms could be an early sign of Reye’s syndrome, a rare but serious illness. A doctor should be consulted before TRIPARC is used in such patients.
Concomitant use of aspirin, as in TRIPARC, with other systemic NSAID’s including cyclooxygenase-2-seletive inhibitors, should be avoided due to the potential for additive undesirable effects (see section 4.5).
Serious hypersensitivity reactions or anaphylaxis can occur, bronchospasm may be precipitated in patients suffering from or with previous history of asthma, allergic disease or nasal polyps.
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 therapy with aspirin as in TRIPARC.
In view of the medicine’s inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.
The risk of PUBs is higher with increasing doses of TRIPARC, in patients with a history of ulcers, and the elderly (see section 4.3).
Gastrointestinal bleeding, ulceration or perforation, which can be fatal have been reported with all NSAID’s and may occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. When gastrointestinal bleeding or ulceration occurs in patients receiving TRIPARC, treatment with TRIPARC should be stopped.
TRIPARC should be given with caution to patients with history of gastrointestinal disease (e.g. ulcerative colitis. Crohn’s disease, hiatus hernia, gastro-oesophageal reflux disease, dyspepsia, angiodysplasia) as the condition may be exacerbated. Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported. TRIPARC 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 containing medicines such as TRIPARC. 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 TRIPARC and evaluate the patient immediately.
Aspirin, as in TRIPARC, decreases platelet adhesiveness and increases bleeding time. Haematological and haemorrhagic effects can occur and may be severe. Patients should report any unusual bleeding symptoms to their healthcare practitioner. Due to its inhibitory effect on platelet aggregation aspirin may cause increased bleeding during and after surgery. As TRIPARC contains aspirin, treatment should be discontinued several days before scheduled surgical procedures.
The use of TRIPARC in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may lead to haemolytic anaemia as more than 1 g aspirin daily may precipitate acute haemolytic anaemia in patients with G6PDH deficiency.
Long term use of TRIPARC may cause iron-deficiency anaemia.
Aspirin as in TRIPARC may interfere with insulin and glucagon control in diabetics.
Aspirin as in TRIPARC can interfere with thyroid function tests.
Persons sensitive to aspirin as in TRIPARC, often have cross-sensitivity to NSAIDs. Some patients, especially those with asthma, chronic urticaria or chronic rhinitis, exhibit notable hypersensitivity to aspirin, which may provoke reactions including urticaria, angioedema, rhinitis and severe even fatal paroxysmal bronchospasm and dyspnoea.
The elderly have an increased frequency of adverse reactions to NSAIDs, including TRIPARC, especially gastrointestinal bleeding and perforation (PUBs), which may be fatal. The risk of gastrointestinal bleeding or perforation (PUBs) is higher with increasing doses of TRIPARC, in patients with a history of ulcers, and the elderly.
Regular use of NSAIDs such as TRIPARC 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 (see section 4.6).
The use of NSAIDs, such as aspirin, as in TRIPARC, around 20 weeks gestation or later in pregnancy may cause foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
Healthcare professionals should consider ultrasound monitoring of amniotic fluid if TRIPARC treatment extends beyond 48 hours. Discontinue TRIPARC if oligohydramnios occurs and follow up according to clinical practice.
TRIPARC contains paracetamol. Do not use with any other paracetamol containing medicines. Concomitant use with other medicines containing paracetamol may lead to an overdose. Paracetamol overdose may cause liver failure which may require liver transplant or lead to death.
The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. Patients suffering from hepatic or renal disease should take paracetamol under medical supervision.
Underlying liver disease increases the risk of paracetamol related liver damage. The overall benefit-risk should be considered in patients diagnosed with liver or kidney impairment before use.
Cases of hepatic failure have been reported in patients with depleted glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index or are chronic heavy users of alcohol or have sepsis.
In patients with glutathione depleted states, the use of paracetamol as in TRIPARC may increase the risk of metabolic acidosis.
Paracetamol as in TRIPARC, should also be given with care to patients with alcohol dependence, chronic malnutrition, or dehydration.
Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), exfoliative dermatitis, 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, as contained in TRIPARC. If a patient develops SCAR, skin rash, mucosal lesions or other signs of hypersensitivity, treatment with TRIPARC must immediately be discontinued and appropriate treatment instituted.
Excess intake of caffeine (e.g. tea, coffee and some canned drinks) should be avoided while taking TRIPARC.
TRIPARC should not be used in children under the age of 12 (see section 4.3). There is an association between aspirin and Reye’s syndrome when given to children and teenagers during or immediately after a viral illness (such as chickenpox and influenza). Reye’s syndrome is a rare disease which affects the brain and liver and can be fatal. For this reason, children and teenagers (between 12 and 16 years of age) who have or are recovering from chickenpox or flu-like symptoms should not use this medicine, unless prescribed by a health practitioner (see section 4.3).
Aspirin, paracetamol and caffeine combination medicines, such as TRIPARC, should not be used together with other non-steroidal anti-inflammatory drugs (NSAIDs) including acetylsalicylic acid and cyclo-oxygenase-2-specific inhibitors as these may increase the risk of adverse effects. Aspirin, paracetamol and caffeine combination medicines should be used with caution when taken in combination with the following medicines as interactions have been reported.
Use of two or more NSAIDs concomitantly could result in an increase in undesirable effects.
Concurrent use of other NSAIDs or corticosteroids may increase the likelihood of GI side effects including perforation, ulceration and bleeding (PUB). Aspirin as in TRIPARC may decrease the plasma concentration of some other NSAIDs, for example, indomethacin, and piroxicam.
Antagonism of the diuretic effect. There is a risk of a reduced diuretic effect especially in patients with existing renal or cardiovascular disease.
Aspirin, as in TRIPARC, can reduce antihypertensive effect of beta-blockers.
TRIPARC may enhance the effects of anticoagulants such as coumarins (e.g. warfarin) and heparin, and of platelet aggregation inhibitors such as ticlopidine, clopidogrel, and cilostazol, as there is an increased risk of bleeding. Clinical and laboratory monitoring of the bleeding time and prothrombin time should be performed.
There is an increased risk of bleeding. Particularly treatment with TRIPARC should not be initiated within the first 24 hours after treatment with alteplase in acute stroke patients. Concomitant use is therefore not recommended.
Aspirin, as in TRIPARC diminishes the effects of antigout preparations such as probenecid and sulphinpyrazone, due to inhibition of tubular resorption, leading to high plasma levels of aspirin.
Aspirin, as in TRIPARC, may reduce their activity due to competition and inhibition of urinary prostaglandins. NSAIDs can cause acute kidney failure, especially in dehydrated patients. If a diuretic is administered simultaneously with aspirin, as in TRIPARC, it is necessary to ensure adequate hydration of the patient to monitor the kidney function and blood pressure, particularly when starting diuretic treatment.
Metoclopramide increases the rate of absorption of aspirin, as in TRIPARC. However, concurrent use need not be avoided.
The effect of phenytoin may be enhanced by aspirin, as in TRIPARC. Aspirin increases serum levels of phenytoin. Serum phenytoin should be well monitored.
The effect of valproate may be enhanced by aspirin, as in TRIPARC. Aspirin inhibits its metabolism and hence could increase its toxicity Valproate levels should be well monitored.
Delayed excretion and increased toxicity of methotrexate. In case of concomitant use with TRIPARC, renal function should be monitored.
Some of the side effects of aspirin, as in TRIPARC, on the gastrointestinal tract are enhanced by alcohol. Co-administration of alcohol and aspirin increases the risk of gastrointestinal haemorrhage.
Use of gold compounds with aspirin, as in TRIPARC may exacerbate aspirin-induced liver damage.
Use of aspirin, as in TRIPARC, with dipyridamole may result in an increase in plasma-salicylate concentrations.
May also increase peak plasma-salicylate concentrations.
Concomitant use of aspirin with diuretics or antihypertensive medicines (e.g. beta blockers, angiotensin converting enzyme (ACE) inhibitors) may cause a decrease in their antihypertensive effect. Therefore, the combination should be administered with caution and patients, especially the elderly, should have their blood pressure periodically monitored. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter, particularly for diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity. Concomitant treatment with potassium-sparing medicines may be associated with increased serum potassium levels, which should therefore be monitored frequently.
Salicylate intoxication has occurred in patients on high-dose salicylate regimens (aspirin as in TRIPARC) and carbonic anhydrase inhibitors.
Antacids may increase the excretion of aspirin by alkalinisation of urine.
Aspirin, as in TRIPARC, may enhance the activity of oral antidiabetic medicines and sulphonamides, thus some downward readjustment of the dosage of the antidiabetic may be appropriate if large doses of salicylates are used. Increased blood glucose controls are recommended.
Aspirin, as in TRIPARC, may increase the activity of sulfonylurea hypoglycaemic medication and zafirlukast. Aspirin, as in TRIPARC, diminishes the effects of uricosurics such as probenecid and sulfinpyrazone.
May mask the respiratory symptoms of aspirin, as in TRIPARC, overdosage and have been reported to enhance its toxicity.
Increase risk of gastrointestinal bleeding.
Reduces the liver’s capacity to deal with paracetamol.
The speed of absorption of paracetamol, as in TRIPARC, is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.
The speed of absorption of paracetamol as in TRIPARC is increased by metoclopramide and domperidone. However, concurrent use need not be avoided.
The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol, as in TRIPARC, with increased risk of bleeding; occasional doses have no significant effect.
Increased plasma concentration of chloramphenicol. The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic medications or medications that induce liver microsomal enzymes.
Excretion may be affected and plasma concentrations altered when paracetamol as in TRIPARC is given with probenecid.
Caffeine elimination half-life has been reported to be increased and clearance decreased.
Fluvoxamine reduces the clearance and prolongs the elimination half-life of caffeine, as in TRIPARC.
The mean clearance of caffeine was increased and its half-life decreased in epileptic patients taking phenytoin, resulting in lower plasma-caffeine concentrations.
Allopurinol caused a dose-dependent inhibition of the conversion of 1-methylxanthine to 1-methyluric acid.
Oral cimetidine reduced the systemic clearance of caffeine, as in TRIPARC, and prolonged its elimination half-life in healthy patients.
Methoxsalen reduced the clearance of caffeine, as in TRIPARC, in patients with psoriasis, consistent with a cytochrome P450 isoenzyme CYP1A2-dependant inhibition of caffeine demethylation.
The clearance of caffeine, as in TRIPARC, has been reported to be reduced and its elimination half-life increased in women taking oral contraceptives as well as postmenopausal women given oestrogens for hormone replacement therapy.
Caffeine can increase the elimination of lithium from the body, concomitant use is therefore not recommended.
The safety of TRIPARC in pregnancy and lactation has not been established. TRIPARC is not recommended for use during pregnancy and is contraindicated during the third trimester of pregnancy (see section 4.3).
Pregnant women should seek medical advice before taking TRIPARC.
Aspirin, as in TRIPARC, should be avoided in the first two trimesters of pregnancy unless the potential benefit to the mother outweighs the risk to the foetus in the view of the treating physician. Regular use of NSAIDs such as TRIPARC 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 and a risk of foetal renal impairment with subsequent oligohydramnios.
The onset of labour may be delayed and its duration increased, with increased risk of bleeding tendency in both the mother and child. If the expected benefit to the mother is greater than the possible risk to the foetus, the lowest effective dose and the shortest duration of treatment should be considered.
Caffeine is not recommended for use during pregnancy due to the possible increased risk of spontaneous abortion associated with caffeine consumption.
TRIPARC is not recommended for use during breastfeeding.
There is insufficient information on the effects of aspirin at low concentration in infants (see section 4.3).
Aspirin, as in TRIPARC, is secreted into breast milk in low concentrations, and regular high doses may affect neonatal clotting.
Treatment should be avoided during breastfeeding because of the possible risk of Reye’s syndrome and the potential impairment of platelet function in the infant, as well as neonatal bleeding due to hypoprothrombinaemia.
Paracetamol, as in TRIPARC, is excreted in breastmilk but not in a significant amount at recommended dosages.
Caffeine, as in TRIPARC, appears in breast milk. Caffeine in breastmilk may potentially have a stimulating effect on breast fed infants but significant toxicity has not been observed. Irritability and poor sleeping pattern in the infant can occur.
There is no fertility data.
TRIPARC has a no or negligible influence on the ability to drive and use machines.
Since adverse reactions such as dizziness, headache and vertigo have been reported in patients receiving TRIPARC, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that TRIPARC does not adversely affect their ability to do so (see section 4.4 and/or 4.8).
Paracetamol:
| System organ class | Less frequent | Frequency unknown (cannot be estimated from the available data) |
|---|---|---|
| Blood and the lymphatic system disorders | Haematological reactions including thrombocytopenia, leucopenia, pancytopenia, neutropenia, agranulocytosis | |
| Immune system disorders | Anaphylaxis, cutaneous hypersensitivity reactions including rashes, angioedema | |
| Respiratory, thoracic and mediastinal disorders | Bronchospasm*1 | |
| Gastrointestinal disorders | Pancreatitis, nausea, vomiting | |
| Hepato-biliary disorders | Hepatitis, hepatic necrosis, increased levels of transaminases, hepatic failure | |
| Skin and subcutaneous tissue disorders | Dermatitis, skin rashes, other hypersensitivity reactions2 | Severe cutaneous adverse reactions (SCARs) such as Stevens Johnson syndrome/toxic epidermal necrolysis, acute generalised exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS), fixed drug eruption (FDE) (see section 4.4)* |
| Renal and urinary disorders | Renal colic, renal failure and sterile pyuria |
* Post marketing data.
1 There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.
2 The rash is usually erythematous or urticarial but sometimes more serious and may be accompanied by fever and mucosal lesions.
Aspirin:
| System organ class | Frequent | Less frequent | Frequency unknown (cannot be estimated from the available data) |
|---|---|---|---|
| Blood and the lymphatic system disorders | Prolonged use of high doses may lead to iron- deficiency anaemia, blood dyscrasias, gastrointestinal haemorrhage1 | Prolonged bleeding time, thrombocytopenia, ecchymosis | |
| Immune system disorders | Hypersensitivity reactions including, anaphylaxis angioedema, severe bronchoconstriction, paroxysmal bronchospasm, dyspnoea, skin eruptions (especially in persons with asthma, chronic urticaria and rhinitis) | ||
| Metabolism and nutrition disorders | Sodium and fluid retention | ||
| Nervous system disorders | Mental confusion, dizziness | ||
| Ear and labyrinth disorders | Hearing disturbances (such as tinnitus), vertigo, temporary hearing loss | ||
| Cardiac disorders | Oedema, cardiac failure | ||
| Vascular disorders | Hypertension | ||
| Respiratory, thoracic and mediastinal disorders | Rhinitis2 | Bronchospasm in patients sensitive to aspirin and other NSAIDs | |
| Gastrointestinal disorders3 | Nausea, vomiting, diarrhoea, flatulence, dyspepsia | Peptic ulcers, perforation, peptic ulceration and gastrointestinal bleeding (PUBs), sometimes fatal, constipation, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis, Crohn’s disease, gastritis | |
| Hepato-biliary disorders | Reye’s Syndrome (in children under 16), elevation in transaminase levels | ||
| Skin and subcutaneous tissue disorders | Urticaria, other skin eruptions, skin reactions | Skin eruptions, 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 | Renal papillary necrosis | Renal dysfunction, increased blood uric acid levels | |
| Reproductive system and breast disorders | Prolonged pregnancy and labour, peripartum bleeding |
1 Prolonged bleeding time, and bleeding disorders, such as epistaxis, purpura and intracranial haemorrhage may occur.
2 Some persons especially asthmatics, exhibit notable sensitivity to aspirin which may provoke various hypersensitivity reactions which may include skin eruptions, paroxysmal bronchospasm and dyspnoea. Worsening of asthma may occur.
Caffeine:
| System organ class | Frequent | Less frequent | Frequency unknown (cannot be estimated from the available data) |
|---|---|---|---|
| Psychiatric disorders | Insomnia, restlessness, anxiety and irritability, nervousness | ||
| Nervous system disorders | Stimulation of the central nervous system with anxiety, restlessness, vertigo, tremor (high doses) | Headache, dizziness | |
| Cardiac disorders | Palpitation (high doses) | ||
| Gastrointestinal disorders | Gastrointestinal irritation with vomiting, abdominal pain | Gastrointestinal bleeding | Nausea, increased gastric secretions, may cause gastric ulceration, gastrointestinal disturbances |
When the recommended aspirin-caffeine dosing regimen is combined with dietary caffeine intake, the resulting higher dose of caffeine may increase the potential for caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headaches, gastrointestinal disturbances and palpitations.
Caffeine increases gastric secretions and may cause gastric ulceration.
Adverse events due to caffeine are more likely to occur with increasing dose and duration of use.
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA: https://www.sahpra.org.za/Publications/Index/8.
Aspen Pharmacare:
E-mail: Drugsafety@aspenpharma.com
Tel: 0800 118 088
Not applicable.
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