No-spa^® (Tablets, Solution) Instructions for Use

ATC Code

A03AD02 (Drotaverine)

Active Substance

Drotaverine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Spasmolytic drug

Pharmacotherapeutic Group

Spasmolytic agent

Pharmacological Action

Pharmacodynamics

Drotaverine is an isoquinoline derivative that exhibits a powerful spasmolytic effect on smooth muscle by inhibiting the enzyme phosphodiesterase type 4 (PDE4). Inhibition of the PDE4 enzyme leads to an increase in cAMP concentration and inactivation of myosin light chain kinase, which subsequently causes relaxation of smooth muscle.

The effect of drotaverine, which reduces the concentration of Ca²⁺ ions via cAMP, explains the antagonistic effect of drotaverine in relation to Ca²⁺ ions.

In vitro, Drotaverine inhibits the PDE4 enzyme without inhibiting PDE3 and PDE5 enzymes. Therefore, the efficacy of drotaverine depends on the concentrations of PDE4 in different tissues. PDE4 is most important for suppressing the contractile activity of smooth muscle, which is why selective inhibition of PDE4 can be useful for treating hyperkinetic dyskinesias and various diseases accompanied by spastic conditions of the gastrointestinal tract.

The hydrolysis of cAMP in the myocardium and vascular smooth muscle occurs mainly with the help of the PDE3 enzyme, which explains the fact that with high spasmolytic activity, drotaverine lacks serious side effects from the heart and blood vessels and pronounced effects on the cardiovascular system.

Drotaverine is effective for spasms of smooth muscle of both neurogenic and muscular origin. Regardless of the type of autonomic innervation, Drotaverine relaxes the smooth muscle of the gastrointestinal tract, biliary tract, and genitourinary system.

Due to its vasodilating action, Drotaverine improves blood supply to tissues. Thus, the above-described mechanisms of action of drotaverine eliminate smooth muscle spasm, which leads to pain reduction.

Pharmacokinetics

Absorption

Compared to papaverine, Drotaverine is absorbed faster and more completely from the gastrointestinal tract when taken orally. After presystemic metabolism, 65% of the taken dose of drotaverine enters the systemic bloodstream. C_max of drotaverine in blood plasma is reached within 45-60 minutes.

Distribution

In vitro, Drotaverine has a high binding to plasma proteins (95-98%), especially to albumin, γ- and β- globulins.

Drotaverine is evenly distributed in tissues and penetrates smooth muscle cells. It does not penetrate the blood-brain barrier. Drotaverine and/or its metabolites may slightly penetrate the placental barrier.

Metabolism

Drotaverine is almost completely metabolized in the liver.

Excretion

T_1/2 of drotaverine is 8-10 hours.

Within 72 hours, Drotaverine is almost completely eliminated from the body. About 50% of drotaverine is excreted by the kidneys and about 30% through the gastrointestinal tract. Drotaverine is mainly excreted in the form of metabolites; the unchanged form of drotaverine is not detected in urine.

Indications

• Spasms of smooth muscle in diseases of the biliary tract (cholecystolithiasis, cholangiolithiasis, cholecystitis, pericholecystitis, cholangitis, papillitis);
• Spasms of smooth muscle of the urinary tract (nephrolithiasis, ureterolithiasis, pyelitis, cystitis, bladder spasms).

As auxiliary therapy

• For spasms of smooth muscle of the gastrointestinal tract (gastric and duodenal ulcer, gastritis, spasms of the cardia and pylorus, enteritis, colitis, spastic colitis with constipation, irritable bowel syndrome with flatulence);
• For tension headaches;
• For dysmenorrhea (menstrual pain).

ICD codes

Dosage Regimen

Tablets

Adults

Take orally. 1-2 tablets per dose 2-3 times/day. The maximum daily dose is 6 tablets (which corresponds to 240 mg).

Children

Clinical studies on the use of drotaverine in children have not been conducted.

In case of prescribing drotaverine to children

• from 6 to 12 years 1 tablet 1-2 times/day. Maximum daily dose – 2 tablets (which corresponds to 80 mg);
• over 12 years 1 tablet 1-4 times/day or 2 tablets 1-2 times/day. Maximum daily dose – 4 tablets (which corresponds to 160 mg).

When taking the drug without consulting a doctor, the recommended duration of use is usually 1-2 days. In cases where Drotaverine is used as auxiliary therapy, the duration of treatment without consulting a doctor may be 2-3 days. If the pain syndrome persists, the patient should consult a doctor.

Method of efficacy assessment

If the patient can easily self-diagnose the symptoms of their disease, as they are well-known to them, then the effectiveness of the treatment, namely the disappearance of pain, is also easily assessed by the patient. If within a few hours after taking the maximum single dose there is a moderate reduction in pain or no reduction in pain, or if the pain does not significantly decrease after taking the maximum daily dose, it is recommended to consult a doctor.

When using a bottle with a polyethylene stopper equipped with a unit-dose dispenser: before use, remove the protective strip from the top of the bottle and the sticker from the bottom of the bottle. Place the bottle in the palm so that the dispensing hole on the bottom does not rest against the palm. Then press on the top of the bottle, as a result of which one tablet will fall out of the dispensing hole on the bottom.

Solution

Adults

The average daily dose is 40-240 mg of drotaverine hydrochloride (divided into 1-3 doses/day) intramuscularly.

For acute colic (renal or biliary) – 40-80 mg intravenously slowly (duration of administration approximately 30 seconds).

Adverse Reactions

The following adverse reactions observed in clinical studies are divided by organ systems with an indication of the frequency of their occurrence in accordance with the following gradations recommended by WHO: very common (≥10%), common (≥1%, <10%); uncommon (≥0.1%, <1%); rare (≥0.01%, <0.1%), very rare, including isolated reports (<0.01%), frequency unknown (cannot be estimated from the available data).

Nervous system disorders rare – headache, vertigo, insomnia; frequency unknown – dizziness.

Cardiac and vascular disorders rare – palpitations, decreased blood pressure.

Gastrointestinal disorders rare – nausea, constipation.

Immune system disorders rare – allergic reactions (angioedema, urticaria, rash, itching) (see section "Contraindications").

Contraindications

• Severe hepatic or renal impairment;
• Severe heart failure (low cardiac output syndrome);
• Children under 6 years of age;
• Breastfeeding period (lack of clinical data);
• Hereditary galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (due to the presence of lactose monohydrate in the drug composition);
• Hypersensitivity to the active substance or to any of the excipients of the drug.

With caution arterial hypotension, pregnancy, children.

Use in Pregnancy and Lactation

Conducted studies have not revealed teratogenic and embryotoxic effects of drotaverine, as well as adverse effects on the course of pregnancy. However, if it is necessary to use the drug No-spa^® during pregnancy, caution should be exercised and the drug should be prescribed only after assessing the ratio of potential benefit for the mother and possible risk for the fetus.

Due to the lack of animal studies and clinical data, it is not recommended to prescribe Drotaverine during breastfeeding.

Use in Hepatic Impairment

The use of the drug is contraindicated in severe hepatic impairment.

Use in Renal Impairment

The use of the drug is contraindicated in severe renal impairment.

Pediatric Use

The use of the drug is contraindicated in children under 6 years of age.

Special Precautions

Each tablet of the drug No-spa^® 40 mg contains 52 mg of lactose monohydrate. This may cause gastrointestinal complaints in patients with lactose intolerance. This form is unacceptable for patients with lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome (see section "Contraindications").

Effect on ability to drive vehicles and mechanisms

When taken orally in therapeutic doses, Drotaverine does not affect the ability to drive a car and perform work requiring increased attention. If any side effects occur, the issue of driving vehicles and working with mechanisms requires individual consideration. In case of dizziness after taking the drug, potentially hazardous activities such as driving vehicles and working with mechanisms should be avoided.

Overdose

Symptoms overdose of drotaverine has been associated with cardiac rhythm and conduction disorders, including complete bundle branch block and cardiac arrest, which can be fatal.

Treatment in case of overdose, patients should be under close medical supervision; symptomatic therapy and treatment aimed at maintaining basic body functions are carried out, including artificial induction of vomiting and gastric lavage.

Drug Interactions

PDE inhibitors, like papaverine, weaken the antiparkinsonian effect of levodopa. When prescribing drotaverine simultaneously with levodopa, an increase in rigidity and tremor is possible.

With simultaneous use with other spasmolytic agents, including m-anticholinergics, mutual enhancement of the spasmolytic effect is possible.

Storage Conditions

The drug should be stored out of the reach of children, PVC/PVDC/Aluminum blisters – at a temperature not exceeding 30°C (86°F), Aluminum/Aluminum (polymer laminated) blisters – at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use the drug after the expiration date indicated on the packaging.

Dispensing Status

The drug is dispensed without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.