SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Askit Powders

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Acetylsalicylic acid    530.0 mg

Aloxiprin    140.0    mg

Caffeine Citrate    110.0    mg

For a full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Powder

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Recommended clinical indications.

The relief of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains, aches and pains.

The symptomatic relief of influenza, feverishness, feverish colds

The symptomatic relief of sprains, rheumatic pain, backache, sciatica, lumbago, fibrositis, muscular aches and pains, joint swelling and stiffness.

4.2 Posology and method of administration

Oral.

Adults:

One powder at 4 hourly intervals until symptoms subside. Maximum dose 6 powders in 24 hours.

Elderly:

No special dosage requirements.

Children:

Do not give to children under 16 years, unless specifically indicated (e.g. Kawasaki’s disease).

Powder to be dispersed in water or swallowed with a draught of water.

4.3    Contraindications

Acetylsalicylic acid must not be used in the following cases:

•    hypersensitivity to acetylsalicylic acid or other salicylates, or to any other components of the product,

•    a history of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory drugs,

•    acute gastrointestinal ulcers,

•    haemorrhagic diathesis,

•    severe renal failure,

•    severe hepatic failure,

•    severe cardiac failure,

•    in combination with methotrexate at doses of 15 mg/week or more (see interactions with other medicinal products and other forms of interaction),

•    third trimester of pregnancy.

4.4    Special warnings and precautions for use

Acetylsalicylic acid should be used with particular caution in the following cases:

•    hypersensitivity to analgesics / anti-inflammatory agents / anti-rheumatics and in the presence of other allergies,

•    history of gastro-intestinal ulcers including chronic or recurrent ulcer disease or history of gastro-intestinal bleeding,

•    with concomitant treatment with anticoagulants (see interactions with other medicinal products and other forms of interaction),

• patients with impaired renal function or patients with impaired cardiovascular circulation (e.g. renal vascular disease, congestive heart failure, volume depletion, major surgery, sepsis or major haemorrhagic events), since acetylsalicylic acid may further increase the risk of renal impairment,

•    impaired hepatic function.

Acetylsalicylic acid may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions. Risk factors are pre-existing asthma, hay fever, nasal polyps, or chronic respiratory disease. This also applies to patients exhibiting allergic reactions (e.g. cutaneous reactions, itching, urticaria) to other substances.

Due to its inhibitory effect on platelet aggregation which persists for several days after administration, acetylsalicylic acid may lead to an increased bleeding tendency during and after surgical operations (including minor surgeries, e.g. dental extractions).

At low doses, acetylsalicylic acid reduces the excretion of uric acid. This can possibly trigger gout attacks in predisposed patients.

There is a possible association between aspirin and Reye’s Syndrome when given to children. Reye’s Syndrome is a very rare disease which affects the brain and liver and can be fatal. For this reason aspirin should not be given to children under 16, unless specifically indicated (e.g. Kawasaki’s disease).

In patients suffering from severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, acetylsalicylic acid may induce haemolysis or haemolytic anaemia. Factors that may increase the risk of haemolysis are high dosage, fever, or acute infections, for example.

4.5 Interaction with other medicinal products and other forms of interaction

Contraindicated Interactions:

Methotrexate used at doses of 15 mg/week or more:

Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory agents in general and displacement of methotrexate from its plasma protein binding by salicylates) (see section 4.3 Contraindications).

Combinations requiring precautions for use:

Methotrexate, used at doses of less than 15 mg/week:

Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory agents in general and displacement of methotrexate from its plasma protein binding by salicylates).

Anticoagulants, thrombolytics/other inhibitors of platelet aggrega-tion/haemostasis:

Increased risk of bleeding.

Other non-steroidal anti-inflammatory drugs with salicylates at higher doses: Increased risk of ulcers and gastrointestinal bleeding due to synergistic effect.

Selective Serotonin Re-uptake Inhibitors (SSRIs):

Increased risk of upper gastrointestinal bleeding due to possibly synergistic effect Digoxin:

Plasma concentrations of digoxin are increased due to a decrease in renal excretion. Antidiabetics, e.g. insulin, sulphonylureas:

Increased hypoglycemic effect by high doses of acetylsalicylic acid via hypoglycaemic action of acetylsalicylic acid and displacement of sulphonylurea from its plasma protein binding.

Diuretics in combination with acetylsalicylic acid at higher doses:

Decreased glomerular filtration via decreased renal prostaglandin synthesis.

Systemic glucocorticoids, except hydrocortisone used as replacement therapy in Addison's disease:

Decreased blood salicylate levels during corticosteroid treatment and risk of salicylate overdose after this treatment is stopped via increased elimination of salicylates by corticosteroids.

Angiotensin converting enzyme inhibitors (ACE) in combination with acetyl-salicylic acid at higher doses:

Decreased glomerular filtration via inhibition of vasodilatory prostaglandins. Furthermore, decreased antihypertensive effect.

Valproic acid and Phenytoin:

Increased toxicity of valproic acid due to displacement from protein binding sites. Phenytoin is also extensively bound to plasma proteins therefore it can be displaced by acetylsalicylic acid from plasma binding.

Alcohol:

Increased damage to gastro-intestinal mucosa and prolonged bleeding time due to additive effects of acetylsalicylic acid and alcohol.

Uricosurics such as benzbromarone, probenecid:

Decreased uricosuric effect (competition of renal tubular uric acid elimination).

4.6 Fertility, pregnancy and lactation Pregnancy

Doses of 500 mg/day and above:

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre-and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, acetyl salicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:

-    cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

-    renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;

the mother and the neonate, at the end of pregnancy, to:

-    possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.

-    inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.

Lactation

Salicylates and its metabolites pass into breast milk in small quantities.

Since no adverse effects on the infant have been observed so far after shortterm use, interruption of breast-feeding is usually unnecessary. However, on regular use or on intake of high doses, breast feeding should be discontinued early.

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

The listed adverse drug reactions are based on spontaneous reports, thus an organization according to CIOMS III categories of frequency is not possible.

Blood and lymphatic system disorders

In the context of bleeding: haemorrhagic anaemia, iron deficiency anaemia with the respective laboratory and clinical signs and symptoms. In the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency: haemolysis, haemolytic anaemia.

Immune system disorders

Hypersensitivity, drug hypersensitivity, allergic edema and angioedema, anaphylactic reaction, anaphylactic shock with respective laboratory and clinical manifestations

Nervous system disorders

Cerebral and intracranial haemorrhage, dizziness

Ear and labyrinth disorders

Tinnitus

Cardiac disorders

In the context of severe allergic reactions: cardio-respiratory distress Vascular disorders

Haemorrhage, perioperative haemorrhage, haematoma, muscle haemorrhage

Respiratory, thoracic and mediastinal disorders

Epistaxis, analgesic asthma syndrome, rhinitis, nasal congestion

Gastrointestinal disorders

Dyspepsia, gastrointestinal pain, abdominal pain, gingival bleeding, gastrointestinal inflammation, gastrointestinal ulcer, gastrointestinal haemorrhage, gastrointestinal ulcer perforation with the respective laboratory and clinical signs and symptoms, constipation

Hepatobiliary disorders

Liver disorder, transaminases increased

Skin and subcutaneous tissue disorders

Rash, urticaria, pruritus

Renal and urinary disorders

Impaired renal function

Injury, poisoning and procedural complications

See overdose section

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Gastric lavage, forced alkaline diuresis and supportive therapy may be employed. Restoration of acid-base balance may be necessary.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:

Acetylsalicylic acid: nervous system, other analgesics and antipyretics -acetylsalicylic acid, ATC code: N02BA01

Aloxiprin: nervous system, other analgesics and antipyretics - aloxiprin, ATC code: N02BA02

Caffeine citrate: nervous system, psychostimulants, agents used for ADHD and nootropics - caffeine, ATC code: N06BC01

5.2 Pharmacokinetic properties

The biological half life of aspirin is reported as 2 to 3 hours after a single small dose, but appears to be nearer 10 hours after multiple 1g doses. Amounts of total salicylate in urine corresponding to approximately 1, 5 and 13% of ingested dose were excreted during periods of 30 minutes, 1 hour and 2 hours after the oral administration of aspirin and during 1, 2 and 3 hours after aloxiprin. The aspirin of aloxiprin dissolves more slowly in acid solution (ph2) than aspirin i.e. almost 100% aspirin and 20% aloxiprin within 30 minutes. The total amount of salicylate excreted over 24 hours from aspirin and from aloxiprin does not differ appreciably thus indicating the whole of the aspirin of aloxiprin becomes available.

5.3 Preclinical safety data

The preclinical safety profile of acetylsalicylic acid is well documented.

In animal studies, salicylates caused kidney damage at high dosages but no other organic lesions. Acetylsalicylic acid has been extensively studied in vitro and in vivo for mutagenicity; no relevant evidence of a mutagenic potential was found. The same applies to carcinogenicity studies.

Salicylates have exhibited teratogenic effects in animal studies and a number of different species. Implantation disorders, embryotoxic and foetotoxic effects and impairment of learning ability in the offspring after prenatal exposure have been described.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lactose

Sodium lauryl sulphate Colloidal anhydrous silica

6.2 Incompatibilities

None.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 25°C. Protect from moisture.

6.5 Nature and contents of container

Sachet formed from 58gsm machine grade bleached kraft paper and 12 micron polyethylene. Sachets are then placed in card cartons.

Wood free white paper 65g/m2, non toxic for pharmaceutical products. Wrapped powders in card carton overwrapped with polypropylene film.

Pack sizes: 4, 8.