-          Mild-to-moderate pain,
e.g., headache, toothache, period pain, painful symptoms associated with colds (e.g., headache, sore throat and limb pain)

-          Fever

 

Posology

 

Unless otherwise prescribed, the usual dose is:

 

Age	Single dose	Total daily dose
Adolescents aged 16 years and above and adults	1–2 effervescent tablets (equivalent to 400‑800 mg acetylsalicylic acid and 240‑480 mg ascorbic acid)	3–6 effervescent tablets (equivalent to 1,200‑2,400 mg acetylsalicylic acid and 720‑1,440 mg ascorbic acid)

 

If required, single doses can be taken up to 3 times daily at intervals of 4–8 hours.

The total daily dose must not be exceeded.

 

Method of administration

 

The tablets are taken dissolved in water. Do not take on an empty stomach. Aspirin-C should not be used for longer than 4 days without seeking medical advice.

 

Pediatric population

Acetylsalicylic acid may be used in children and adolescents under 16 years only if prescribed by a doctor.
 

Patients with hepatic impairment

Acetylsalicylic acid should be used with caution in patients with hepatic impairment (see section 4.4).

 

Patients with renal impairment

Acetylsalicylic acid should be used with caution in patients with renal impairment (see section 4.4).

 

- Hypersensitivity to acetylsalicylic acid, other salicylates, ascorbic acid, or to any of the excipients listed in section 6.1 - History of asthma attacks triggered by administration of salicylates or substances with a similar effect, in particular non-steroidal anti-inflammatory drugs - Acute gastrointestinal ulcers - Hemorrhagic diathesis - Liver and kidney failure - Severe, uncontrolled heart failure - In combination with methotrexate at a dose of 15 mg or more per week (see section 4.5) - Last trimester of pregnancy (see section 4.6) - Nephrolithiasis or history of nephrolithiasis - Hyperoxaluria - Hemochromatosis

Relating to acetylsalicylic acid

-       Hypersensitivity to other analgesics/anti-inflammatory drugs/antirheumatics or other allergens (see section 4.3)

-       In the presence of allergies (e.g., with skin reactions, itching, hives), asthma, hay fever, swelling of the nasal mucous membranes (nasal polyps), or chronic respiratory diseases

-       Concomitant anticoagulant therapy (see section 4.5)

-       History of gastrointestinal ulcers or bleeding

-       Impaired hepatic function

-       Patients with impaired renal function or reduced cardiovascular blood flow (e.g., renal vascular disease, congestive heart failure, volume depletion, major surgery, sepsis or severe bleeding events): acetylsalicylic acid may further increase the risk of impaired renal function and acute kidney failure

-       Prior to surgery (including minor procedures such as tooth extractions): there may be an increased bleeding tendency

-       Patients with severe glucose-6-phosphate dehydrogenase deficiency: acetylsalicylic acid may induce hemolysis or hemolytic anemia. The risk of hemolysis may be increased by factors such as high dosage, fever or acute infections

-          Curcumin can increase risk of bleeding. Consult a healthcare professional prior to use curcumin if you are taking antiplatelet medication or anticoagulants.

 

 

What else must you consider?

Aspirin-C contains 466.4 mg sodium per effervescent tablet, equivalent to 23 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. Aspirin-C is rich in sodium. This is to be taken into consideration in patients on a sodium-controlled diet (low-sodium/low-salt diet).

 

Taking painkillers for prolonged periods can cause headaches, resulting in more painkillers being taken, which can result in persistence of headaches.

 

Habitual use of painkillers can result in permanent damage to the kidneys with the risk of kidney failure (analgesic nephropathy). This risk is particularly high if several different analgesics are taken in combination.

 

At low doses, acetylsalicylic acid reduces uric acid excretion. This may trigger a gout attack in patients who already have a tendency to low urine excretion.

 

Pediatric population

Acetylsalicylic acid should be used in children and adolescents with febrile conditions only on the advice of a physician and only if other measures are not effective. If persistent vomiting occurs in these conditions, this may be a sign of Reye’s syndrome, a very rare but life-threatening condition in which immediate medical treatment is urgently needed.

Potentiation of effects including increased risk of adverse reactions:

-       Anticoagulants/thrombolytic agents: acetylsalicylic acid may increase the risk of bleeding if it has been taken before thrombolytic therapy. Patients who need to undergo thrombolytic treatment must therefore be monitored closely for signs of external or internal bleeding

-       Antiplatelet drugs, e.g., ticlopidine, clopidogrel: increased risk of bleeding

-       Other non-steroidal analgesics/anti-inflammatory drugs (at doses of 3 g or more acetylsalicylic acid per day): increased risk of gastrointestinal ulcers and bleeding

-       Systemic glucocorticoids (with the exception of hydrocortisone as replacement therapy in Addison's disease): increased risk of gastrointestinal adverse effects

-       Alcohol: increased risk of gastrointestinal ulcers and bleeding

-       Digoxin: increase in plasma concentrations

-       Antidiabetics: blood glucose levels may drop

-       Methotrexate: reduction in excretion and plasma protein binding displacement caused by salicylates (see section 4.3)

-       Valproic acid: plasma protein binding displacement caused by salicylates

-       Selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding because of synergistic effects

 

Attenuation of effects:

-       Diuretics (at doses of 3 g or more acetylsalicylic acid per day)

-       ACE inhibitors (at doses of 3 g or more acetylsalicylic acid per day)

-       Uricosuric agents (e.g., probenecid, benzbromarone)

-       Deferoxamine: possible cardiac decompensation when co-administered with ascorbic acid due to increased toxicity of iron in tissues, particularly of the heart

 

Interactions of ascorbic acid in laboratory testsVitamin C is a reducing agent (i.e., an electron donor) and can cause chemical interference in laboratory tests involving oxidation-reduction reactions, e.g., analysis of glucose, creatinine, carbamazepine, uric acid in urine, serum and hemoccult test. Vitamin C can interfere in tests in which urine and blood glucose are measured and lead to false measurement results, although vitamin C does not have any influence on blood glucose levels.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.

Data from epidemiological studies indicate an increased risk of miscarriages, cardiac malformations and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiac malformations is increased from less than 1 % to 1.5 %. It is assumed that the risk increases with the dose and duration of use.

In animals, administration of a prostaglandin synthesis inhibitor has resulted in increased pre- and post-implantation losses and embryofetal mortality. Increased incidences of various malformations, incl. cardiovascular malformations, have also been reported in animals following administration of a prostaglandin synthesis inhibitor during organogenesis.

 

Acetylsalicylic acid should not be given during the first and second trimester of pregnancy unless this is clearly necessary. If acetylsalicylic acid is taken by a woman attempting to conceive or already in the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.

 

During the third trimester of pregnancy, exposure to prostaglandin synthesis inhibitors may be associated with the following risks:

·      to the fetus:

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

-   renal dysfunction that may progress to renal failure with oligohydramnios

·      to the mother and newborn child at the end of pregnancy:

-   possible prolongation of bleeding time, an antiplatelet effect that can occur even at very low doses

-   inhibition of contractions leading to delayed or prolonged birth

 

As a consequence, acetylsalicylic acid is therefore contraindicated in the third trimester of pregnancy.

 

Breastfeeding

The active substance acetylsalicylic acid and its degradation products are excreted in breast milk in small amounts. Because there have not been any reports to date of adverse effects on the infant, it is not necessary to stop breastfeeding for occasional use of the recommended dose. Nevertheless, breastfeeding should be stopped in cases of more prolonged use/administration of higher doses.

 

Fertility

There is some evidence that medicines that inhibit cyclooxygenase / prostaglandin synthesis can impair female fertility via an effect on ovulation. This is reversible after discontinuation of treatment.

Acetylsalicylic acid and ascorbic acid have no influence on the ability to drive and use machines.

Acetylsalicylic acid:

The following list of undesirable effects includes all adverse effects that have become known under treatment with acetylsalicylic acid, including those under high-dose long-term therapy in rheumatoid arthritis patients. The frequencies beyond isolated cases relate to short-term use up to maximum daily doses of 3 g acetylsalicylic acid.

 

The assessment of adverse effects is based on the following frequencies:

Very common:                       ³ 1/10

Common:                   ³ 1/100, < 1/10

Uncommon:               ³ 1/1,000, < 1/100

Rare:              ³ 1/10,000, < 1/1,000

Very rare:                  < 1/10,000

Not known:    Cannot be estimated from the available data

 

Blood and lymphatic system disorders:

There have been rare to very rare reports of even serious bleeding events such as cerebral bleeding, particularly in patients with uncontrolled hypertension and/or under concomitant treatment with anticoagulants, which in isolated cases may be life-threatening.

Hemolysis and hemolytic anemia have been reported in patients with severe glucose-6-phosphate dehydrogenase deficiency.

Bleeding, e.g., nosebleeds, bleeding from the gums, bruising or genitourinary bleeding with possible prolongation of the bleeding time (see section 4.4). This effect may persist for 4 to 8 days after intake.

 

Gastrointestinal disorders:

Common:

Gastrointestinal disorders such as heartburn, diarrhea, nausea, vomiting, abdominal pain.

Rare:

Gastrointestinal ulcers, which may very rarely result in perforation.

Gastrointestinal bleeding, which may very rarely result in iron deficiency anemia.

Gastrointestinal inflammation.

Not known:

In the event of prior damage to the intestinal mucosa, multiple membranes can form in the intestinal lumen, potentially resulting in subsequent stenosis (particularly in cases of long-term treatment).

 

Nervous system disorders:

Headache, dizziness, impaired hearing, ringing in the ears (tinnitus) and mental confusion may be signs of an overdose (see section 4.9).

 

Skin and subcutaneous tissue disorders:

Uncommon:

Hypersensitivity reactions, such as skin reactions.

Rare:

Hypersensitivity reactions, such as severe skin reactions (including exudative erythema multiforme).

 

Immune system disorders:

Rare:

Hypersensitivity reactions of the respiratory tract, gastrointestinal tract and cardiovascular system, especially in asthmatic patients.

Possible symptoms are: drop in blood pressure, episodes of dyspnea, rhinitis, nasal congestion, anaphylactic shock or angioedema.

 

Hepatobiliary disorders:

Very rare:

Increases in liver enzyme values.

 

Renal and urinary disorders:

Renal impairment and acute kidney failure have been reported.

 

Ascorbic acid (vitamin C)

The adverse effects listed below are based on "spontaneous reports", and grading according to frequency is therefore not possible (frequency is not known).

 

Immune system disorders:

Hypersensitivity reactions, allergic reaction and anaphylactic shock.

 

Gastrointestinal disorders:

Diarrhea, nausea, vomiting, gastrointestinal pain, abdominal pain.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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:
 

To report any side effect(s):

 

Saudi Arabia

The National Pharmacovigilance Centre (NPC): Fax: +966-11-205-7662 SFDA Call Center: 19999 E-mail: npc.drug@sfda.gov.sa Website: https://ade.sfda.gov.sa/

Salicylate toxicity can result from chronic, therapeutic overdose and from potentially life-threatening acute poisoning (overdose due to inadvertent intake in children, including accidental intoxication).

 

Chronic salicylate poisoning can be insidious, as the signs and symptoms are non-specific. Mild salicylate poisoning generally occurs following repeated intake of high doses (> 100 mg/kg/day over 2 days can be toxic). Symptoms include drowsiness, dizziness, tinnitus, hearing impairment, sweating, nausea and vomiting, headache and confusion and can be controlled by reducing the dose.

 

The main feature of acute poisoning is a severe acid-base imbalance, which can vary with age and the degree of poisoning. The most common sign of acute poisoning in children is metabolic acidosis. The severity of poisoning cannot be assessed on the basis of the plasma concentration alone. The absorption of acetylsalicylic acid can be delayed by reduced gastric emptying, concrement formation in the stomach or as a result of ingestion of gastro-resistant medicinal products. Tinnitus can occur at plasma concentrations of 150 to 300 mcg/mL. Further severe adverse effects can occur at concentrations over 300 mcg/mL.

 

The pathophysiological effects of salicylate poisoning are complex.

 

Mild-to-moderate poisoning manifests as nausea, vomiting, tachypnea, hyperventilation, respiratory alkalosis and diaphoresis.

 

Signs of moderate-to-severe poisoning are: respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, impaired glucose metabolism and ketosis, tinnitus, deafness, gastrointestinal bleeding, respiratory disorders (ranging from hyperventilation to respiratory arrest), cardiovascular disorders (ranging from arrhythmia to cardiovascular shock), fluid and electrolyte disturbances (ranging from dehydration to kidney failure), hematological conditions (ranging from antiplatelet effects to coagulopathy), toxic encephalopathy and CNS depression (ranging from lethargy to coma and seizures).

 

Treatment of acetylsalicylic acid poisoning is guided by the extent, severity, and clinical symptoms and is based on standardized procedures for poisoning. In severe cases, hemodialysis may be necessary. The first emergency measures should be to accelerate the excretion of the drug and to restore the electrolyte and acid-base balance.

 

The literature includes isolated reports of acute and chronic ascorbic acid overdose. In patients with glucose-6-phosphate dehydrogenase deficiency, this may lead to oxidative hemolysis, disseminated intravascular coagulation and significantly elevated oxalate levels in serum and urine.

Elevated oxalate levels may lead to calcium oxalate deposits in dialysis patients.

In addition, some reports show that high doses of ascorbic acid (oral or IV) can cause calcium oxalate deposits, calcium oxalate crystalluria (in patients predisposed to increased crystal aggregation), tubulointerstitial nephropathy and acute renal failure (result of calcium oxalate crystals).

Pharmacotherapeutic group: Nervous system, Other analgesics and antipyretics, Salicylic acid and derivatives, ATC code: N02BA01

 

Acetylsalicylic acid

Acetylsalicylic acid belongs to the group of acid-forming non-steroidal anti-inflammatory drugs with analgesic, antipyretic and anti-inflammatory properties. Its mechanism of action is based on the irreversible inhibition of cyclooxygenase enzymes involved in prostaglandin synthesis.

 

Acetylsalicylic acid at oral doses of between 0.3 and 1.0 g is used to treat mild-to-moderate pain and for increased body temperature, e.g., to reduce temperature in the event of cold or flu and to treat joint and muscle pain.

 

It is also used to treat acute and chronic inflammatory diseases such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.

 

Acetylsalicylic acid also inhibits platelet aggregation by blocking the synthesis of thromboxane A2 in platelets. For this reason, doses of 75 to 300 mg/day are used in various cardiovascular indications.

 

Ascorbic acid

The water-soluble ascorbic acid is part of the body's system of protection against oxygen radicals and other oxidants of endogenous or exogenous origin, which play a particular role in the inflammatory process and in white blood cell function.

Both in vitro and ex vivo experiments show that ascorbic acid has a positive effect on the human leukocyte-mediated immune response.

Ascorbic acid is a key component in the synthesis of intracellular substances (mucopolysaccharides) that, together with collagen fibers, are responsible for sealing the capillary walls.

In clinical trials, when co-administered with acetylsalicylic acid, ascorbic acid displayed evidence of a protective effect in respect of acetylsalicylic acid-induced gastric lesions and oxidative stress

Following oral administration, acetylsalicylic acid is absorbed rapidly and completely from the gastrointestinal tract. During and after absorption, acetylsalicylic acid is converted to its active major metabolite, salicylic acid. Peak plasma levels of acetylsalicylic acid and salicylic acid are reached after 15–30 min and 0.72–2 h respectively. The given durations depend on the pharmaceutical form. The addition of ascorbic acid leads to little or no variability in the PK parameters of acetylsalicylic acid.

Both acetylsalicylic acid and salicylic acid are extensively bound to plasma proteins and rapidly distributed to all parts of the body. Salicylic acid is excreted in breast milk and crosses the placenta.

Salicylic acid is eliminated predominantly by means of metabolism in the liver; the metabolites are salicyluric acid, salicyl phenolic glucuronide, salicylacyl glucuronide, gentisic acid and gentisuric acid.

The elimination kinetics of salicylic acid are dose-dependent, as metabolism is limited by the capacity of the liver enzymes. The elimination half-life therefore varies and is between 2 and 3 h after low doses and up to approximately 15 h after high doses. Salicylic acid and its metabolites are excreted predominantly via the kidneys.

 

The absorption of ascorbic acid (concentration-dependent in the proximal section of the small intestine) is limited. As the single dose increases, bioavailability decreases (60–75 % after 1 g, 16 % after 12 g). The unabsorbed fraction is broken down by the flora in the large intestine, mainly into CO₂ and organic acids. In healthy adults, the maximum metabolic turnover of 40–50 mg/day is reached at plasma concentrations of 0.8–1.0 mg/dL. The total turnover is in the region of 1 mg/day. At extremely high oral doses, plasma concentrations of up to 4.2 mg/dL are achievable in the short-term after 3 h. Under these conditions, ascorbic acid is excreted predominantly (>80 %) unchanged in the urine (half-life 2.9 h). The pool in the body following regular administration of approx. 180 mg/day is at least 1.5 g. Considerable accumulation occurs in the pituitary gland, adrenal glands, eye lenses and white blood cells.

The preclinical safety profile of acetylsalicylic acid is well documented. In animal studies, salicylates have caused kidney damage and gastrointestinal ulcers. Acetylsalicylic acid has undergone suitable mutagenicity and carcinogenicity testing; no relevant evidence of mutagenic or carcinogenic potential has been found.

Salicylates have shown teratogenic effects in a range of animal species. Implantation disorders, embryotoxic and fetotoxic effects and learning impairment in immature animals have been mentioned following prenatal exposure.

Non-clinical studies of acute toxicity, repeated dose toxicity and toxicity to reproduction and development revealed no special hazard for humans.

Isolated positive findings in in vitro genotoxicity studies have not been confirmed in in vivo studies and are not considered to be clinically relevant. 2-year carcinogenicity studies with F344/N rats and B6C3F1 mice yielded no evidence of carcinogenic potential for ascorbic acid.

          sodium dihydrogen citrate, sodium hydrogen carbonate, citric acid, sodium carbonate.

NA

24 months

Not to be stored above 25 °C.

Aspirin-C is a white effervescent tablets with one-side Bayer-cross-embossing.

Package with 10 effervescent tablets is available

NA