Astrapain Forte Tablets

Pain and fever, and pain associated with tension. Short term use in mild to moderate pain associated with anxiety or tension.

Posology
DO NOT EXCEED THE RECOMMENDED DOSE. Not recommended for children under the age of 12 years. Adults: Two tablets every 6 to 8 hours. Not to be used for longer than 10 days. *
Special populations
u2022 Elderly population; dosage should be reduced in debilitated and in elderly patients (see section 4.4).
u2022 Renal impairment; contraindicated in patients with renal insufficiency (see section 4.3).
u2022 Hepatic impairment; contraindicated in patients with hepatic insufficiency (see section 4.3).

• Hypersensitivity to the active substance or to any of the excipients of ASTRAPAIN FORTE TABLETS (see section 6.1).
• It should not be administered to patients with acute intermittent porphyria.
• Patients with renal or hepatic insufficiency.
• Use of ASTRAPAIN FORTE TABLETS during pregnancy should be avoided.
• Asthma, 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.
• Heart failure secondary to chronic lung disease.
• Should not be given during an attack of bronchial asthma, a history of cardiac disease, epilepsy, and all convulsive states.
• Patients taking monoamine oxidase inhibitors or within 14 days of stopping such treatment.
• Porphyria.
• Children under the age of 12 years.
• Women who are breastfeeding their infants and women in the third trimester of pregnancy. (See section 4.6)
• Codeine should not be used at all in children (aged below 18 years) who undergo surgery for the removal of tonsils or adenoids to treat obstructive sleep apnoea, as these patients are more susceptible for respiratory problems.

ASTRAPAIN FORTE TABLETS are not recommended for use by pregnant or breastfeeding women (see section 4.6). Do not use continuously for more than ten days without consulting your doctor. Consult your doctor if no relief is obtained with the recommended dosage. The use of this medicine leads to drowsiness which is aggravated by the simultaneous intake of alcohol and it is dangerous to drive a vehicle or be in charge of machinery while on treatment with this product.

Paracetamol
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 AstraPain Forte Tablets must immediately be discontinued and appropriate treatment instituted (see section 4.8).

Flucloxacillin
Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as those using maximum daily dose of paracetamol. Close monitoring, including measurement of urinary 5 - oxoproline, is recommended.

• Due to the active caffeine, which undergoes extensive metabolism by hepatic microsomal cytochrome P450, ASTRAPAIN FORTE TABLETS is subject to numerous interactions with other medicines which enhance or reduce its metabolic clearance.
• ASTRAPAIN FORTE TABLETS may enhance the sedative effects of central nervous system depressants including alcohol, barbiturates, hypnotics, opioid analgesics.
• ASTRAPAIN FORTE TABLETS has an additive antimuscarinic action with other antimuscarinic medicines such as atropine and antidepressants (both tricyclic and monoamineoxidase inhibitors).
• ASTRAPAIN FORTE TABLETS may enhance the metabolism of oral contraceptives, corticosteroids, phenytoin, phenothiazines and tricyclic antidepressants.
• Paracetamol, as in ASTRAPAIN FORTE TABLETS
  Hepatotoxic medicines u2013 Increased risk of hepatotoxicity. Enzyme inducing medicines u2013 Increased risk of hepatotoxicity. Possible decrease in therapeutic effects of paracetamol.
• Metoclopramide u2013 Absorption of paracetamol may be accelerated.
• Domperidone u2013 Absorption of paracetamol may be accelerated.
• Probenecid u2013 Pre - treatment with probenecid can decrease paracetamol clearance and increase its half - life. Although urinary excretion of the sulphate and glucuronide conjugates of paracetamol are reduced, that of paracetamol is unchanged.
• Cholestyramine u2013 Absorption of paracetamol is reduced if given within one hour of cholestyramine.
• Salicylates - Prolonged concurrent use of paracetamol with salicylates increases the risk of adverse renal effects.
• Antibiotics u2013 Chronic use of isoniazid, an antibiotic medicine often prescribed for tuberculosis, may increase the risk of liver damage when combined with paracetamol, even at recommended doses.
• Warfarin and anticoagulants u2013 Concurrent, chronic, high - dose administration of paracetamol may increase the anticoagulant effect. Paracetamol is recommended as the general analgesic and antipyretic of choice in patients on oral anticoagulant therapy. However, caution is needed since, although it has no effect on the gastric mucosa or on platelet function, some studies (with warfarin, anisindione, dicoumarol, or phenprocoumon) and isolated reports have found an increased risk of bleeding in patients taking regular doses of paracetamol while on an oral anticoagulant. An increase in INR has also been reported in controlled studies of the use of paracetamol in patients stabilised on warfarin. Increased monitoring of anticoagulant therapy may be appropriate for those also taking paracetamol regularly.
• Antibacterials u2013 The plasma - paracetamol concentrations considered an indication for antidote treatment should be halved in patients receiving enzyme inducing drugs such as rifampicin. Severe hepatotoxicity at therapeutic doses or moderate overdoses of paracetamol has been reported in patients receiving isoniazid, alone with other medicines for tuberculosis.
• Antivirals u2013 Severe hepatotoxicity has occurred after use of paracetamol in a patient taking zidovudine and co - trimoxazole. However, neither short - term nor long - term studies (the latter also in an individual patient) have shown any alteration of zidovudine elimination in patients taking zidovudine and paracetamol.
• Interferon - alpha u2013 Paracetamol has also been found to enhance the antiviral effect of interferon alfa.
• Flucloxacillin u2013 Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors (see section 4.4).
• Other medicines u2013 paracetamol is metabolised in the liver and can therefore interact with other medicines that follow the same pathway or may inhibit or may induce this route (e.g. barbiturates, such as phenobarbitone, tricyclic antidepressants, alcohol, carbamazepine).

Pregnancy
ASTRAPAIN FORTE TABLETS should not be used during pregnancy (see section 4.3). This includes maternal use during labour because of the potential for respiratory depression in neonate. Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate. The patient should be advised of the risk of neonatal opioid withdrawal syndrome, and it should be ensured that appropriate treatment will be available.

Breastfeeding
Codeine, as in ASTRAPAIN FORTE TABLETS, should not be used during breastfeeding (see section 4.3), as codeine may be secreted in breast milk and may cause respiratory depression in the infant. At normal therapeutic doses, codeine and its active metabolite may be present in breast milk at very low doses and is unlikely to adversely affect the breast fed infant. However, if the patient is an ultra - rapid metaboliser of CYPD2D6, higher levels of the active metabolite, morphine, may be present in breast milk and on very rare occasions may result in symptoms of opioid toxicity in the infant, which may be fatal.

Fertility
No information available.

The use of this medicine leads to drowsiness which is aggravated by the simultaneous intake of alcohol and it is dangerous to drive a vehicle or be in charge of machinery while on treatment with this product.

Tabulated list of adverse reactions
Body System Undesirable effect Frequent Less frequent Frequency not known
Paracetamol Blood and the lymphatic system disorders: Neutropenia (too few white blood cells) Pancytopenia (too few blood cells of all types) Leucopenia (too few white blood cells) Skin and subcutaneous tissue disorders: Skin rashes and other allergic reactions may occur. This rash is usually erythematous (red skin rash) or urticarial (nettle rash), but sometimes more serious and may be accompanied by fever and mucosal lesions (deterioration of tissue due to injury or disease). Dermatitis, skin rashes, severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Stevens - Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) / drug - induced hypersensitivity syndrome (DIHS) and fixed drug eruption (FDE).
Meprobamate Blood and lymphatic system disorders Agranulocytosis Eosinophilia, Leucopenia, Thrombocytopenia Aplastic anaemia
Cardiac disorders Hypotension Tachycardia Cardiac arrhythmias
Eye disorders Disturbance of vision
Gastrointestinal disorders Nausea Vomiting Diarrhoea
Nervous system disorders Drowsiness Paraesthesia Weakness Headache Paradoxical excitement Dizziness Ataxia
Skin and subcutaneous tissue disorders Hypersensitivity reactions such as skin rashes, urticaria, purpura, angioedema, erythema multiforme and exfoliative or bullous dermatitis may occur. Symptoms of porphyria may be exacerbated.
Other disorders Bronchospasm or anuria
Codeine Cardiac disorders Bradycardia Palpitation Hypotension Orthostatic hypotension Circulatory failure
Gastrointestinal disorders Nausea Vomiting Constipation
Nervous system disorder Vertigo Hyperthermia Restlessness Deepening coma Euphoria Changes of mood Muscle rigidity Drowsiness Confusion Dry mouth Sweating Facial flushing Orthostatic hypotension
Skin and subcutaneous tissue disorders Pruritis Urticaria
Urinary disorders Micturition may be difficult and there may be ureteric or biliary spasms and a diuretic effect.
Other disorders Respiratory depression Raised intracranial pressure and miosis
Caffeine Gastrointestinal disorders Nausea Caffeine increases gastric secretions and may cause gastric ulceration.
Nervous system disorders Headache Insomnia Restlessness Excitement Muscle tremor
Eye disorders Scintillating scotoma
Ear and labyrinth disorders Tinnitus
Cardiac disorders Tachycardia Extrasystoles

Codeine phosphate: Symptoms of overdosage with codeine phosphate include the following: nausea, vomiting, restlessness, sensory disturbances, muscle tremor, diuresis, palpitations, stupor, shock, central stimulation with exhilaration, convulsions, drowsiness, respiratory depression, hypotension with circulatory failure, respiratory collapse, cyanosis and coma. Management: This should include general symptomatic and supportive measures including a clear airway and monitoring of vital signs until stable. Consider activated charcoal if an adult presents within one hour of ingestion of more than 350 mg or a child more than 5 mg/kg. Give naloxone if coma or respiratory depression is present. Naloxone is a competitive antagonist and has a short half - life, so large and repeated doses may be required in a seriously poisoned patient. Observe for at least four hours after ingestion, or eight hours if a sustained release preparation has been taken.

Paracetamol: Prompt treatment is essential. In the event of an overdosage, consult a doctor immediately, or take the person to a hospital directly. 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 - 10 g/day) of paracetamol for several days, in chronic alcoholism, chronic liver disease, AIDS, malnutrition, and with the use of drugs 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: 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 (IV) 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 1000 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, 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. Monitor all patients with significant ingestions for at least ninety six hours. 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. For overdose with an extended/modified release preparation the value of the nomogram is unknown. As there is no information on the plasma levels of paracetamol after an overdose of extended/modified release paracetamol preparations, all patients with suspected or known overdose with such preparations, a level below the u201ctreatment lineu201d of the nomogram may not exclude the possibility of toxicity. Meprobamate: Symptoms are mainly due to the depressant effect on the central nervous system. See also u201cUndesirable effects and Special warnings and precautions for useu201d.