Valoid Injection

In section 3. added Clarity and Color of solution to finished product specifications

In Section6.3  reduction of shelf life of product from four years to two years.

In section 3. added Clarity and Color of solution to finished product specifications

In Section6.3  reduction of shelf life of product from four years to two years.

Section 1, 4.1-4.9, 5.1-5.3, 6.1, 6.3, 6.4-6.6, 9 & 10 of the SmPC were updated.

Section 1, 4.1-4.9, 5.1-5.3, 6.1, 6.3, 6.4-6.6, 9 & 10 of the SmPC were updated.

In section 4.4, the warnings have been updated to include hypotension and transient paralysis.

In section 4.8 there are additional effects listed under nervous system disorders concerning loss of consciousness and transient paralysis. Also agitation has been added as an undesirable effect under psychiatric disorders. Flushing has been added as an undesirable effect following IV administration along with a warning regarding symptoms of overdose following rapid IV doses.

In section 10 the date has been updated to December 2010.

In section 4.4, the warnings have been updated to include hypotension and transient paralysis.

In section 4.8 there are additional effects listed under nervous system disorders concerning loss of consciousness and transient paralysis. Also agitation has been added as an undesirable effect under psychiatric disorders. Flushing has been added as an undesirable effect following IV administration along with a warning regarding symptoms of overdose following rapid IV doses.

In section 10 the date has been updated to December 2010.

Changes related to new quality, pre-clinical, clinical or pharmacovigilance data are noted below in bold.

3.       PHARMACEUTICAL FORM

Solution for Injection (deleted (Injection))

Clear, colourless solution for injection.

4.4.    Special Warnings and Precautions for Use

As with other anticholinergic agents, Valoid may precipate incipient glaucoma and it should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy.  Valoid injection may have a hypotensive effect.

Cyclizine should be used with caution in patients with severe heart failure.  In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure.

Cyclizine should be avoided in porphyria.

There have been reports of abuse of cyclizine, either oral or intravenous for its euphoric or hallucinatory effects. The concomitant misuse of Valoid with large amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine may increase the toxicity of alcohol (see also Section 4.5 interactions).

There have been isolated case reports of transient paralysis occurring in patients using intravenous cyclizine. Two of the patients mentioned in these reports had an underlying neuromuscular disorder.  Thus intravenous cyclizine should be used with caution in all patients in general, and in patients with underlying neuromuscular disorders in particular.

4.8.    Undesirable Effects

Blood and lymphatic system disorders

Agranulocytosis

Cardiac disorders

Tachycardia

Eye disorders

Blurred vision, oculogyration

Gastrointestinal system disorders

Dryness of the mouth, nose and throat, constipation

General disorders and administration site conditions

Asthenia, malaise

Hepatobiliary disorders

Hepatic dysfunction including hepatitis due to hypersensitivity.  Cholestatic jaundice and cholestatic hepatitis have occurred in association with cyclizine.

Immune system disorders

Hypersensitivity reactions, including anaphylaxis, hypersensitivity hepatitis have occurred

Musculoskeletal and connective tissue disorders

Twitching, muscle spasms

Nervous system disorders

Effects on the central nervous system have been reported with cyclizine these include somnolence, headache, dystonia, dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.

There have been rare case reports of patients experiencing depressed levels of consciousness/loss of consciousness. The use of cyclizine has been associated with cases of transient paralysis following administration of the intravenous formulation of the medicine. The onset of paralysis is usually within minutes of administration, affects the limbs, and fully resolves within hours of discontinuation of the medicine (see also Section 4.4 Special Warnings).

Psychiatric disorders

Disorientation, restlessness or agitation, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

Renal and urinary disorders

Urinary retention

Respiratory, thoracic and mediastinal disorders

Bronchospasm, apnoea

Skin and subcutaneous tissue disorders

Urticaria, drug rash, angioedema, allergic skin reactions, fixed drug eruption

Vascular disorders

Hypertension

IV formulation only:

Blisters at the site of injection and pruritus, as well as sensation of heaviness, chills, agitation, flushing and hypotension have been reported.

Rapid IV administration can lead to symptoms similar to overdose.

10.  DATE OF (PARTIAL) REVISION OF TEXT

June 2010

 

Changes related to new quality, pre-clinical, clinical or pharmacovigilance data are noted below in bold.

3.       PHARMACEUTICAL FORM

Solution for Injection (deleted (Injection))

Clear, colourless solution for injection.

4.4.    Special Warnings and Precautions for Use

As with other anticholinergic agents, Valoid may precipate incipient glaucoma and it should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy.  Valoid injection may have a hypotensive effect.

Cyclizine should be used with caution in patients with severe heart failure.  In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure.

Cyclizine should be avoided in porphyria.

There have been reports of abuse of cyclizine, either oral or intravenous for its euphoric or hallucinatory effects. The concomitant misuse of Valoid with large amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine may increase the toxicity of alcohol (see also Section 4.5 interactions).

There have been isolated case reports of transient paralysis occurring in patients using intravenous cyclizine. Two of the patients mentioned in these reports had an underlying neuromuscular disorder.  Thus intravenous cyclizine should be used with caution in all patients in general, and in patients with underlying neuromuscular disorders in particular.

4.8.    Undesirable Effects

Blood and lymphatic system disorders

Agranulocytosis

Cardiac disorders

Tachycardia

Eye disorders

Blurred vision, oculogyration

Gastrointestinal system disorders

Dryness of the mouth, nose and throat, constipation

General disorders and administration site conditions

Asthenia, malaise

Hepatobiliary disorders

Hepatic dysfunction including hepatitis due to hypersensitivity.  Cholestatic jaundice and cholestatic hepatitis have occurred in association with cyclizine.

Immune system disorders

Hypersensitivity reactions, including anaphylaxis, hypersensitivity hepatitis have occurred

Musculoskeletal and connective tissue disorders

Twitching, muscle spasms

Nervous system disorders

Effects on the central nervous system have been reported with cyclizine these include somnolence, headache, dystonia, dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.

There have been rare case reports of patients experiencing depressed levels of consciousness/loss of consciousness. The use of cyclizine has been associated with cases of transient paralysis following administration of the intravenous formulation of the medicine. The onset of paralysis is usually within minutes of administration, affects the limbs, and fully resolves within hours of discontinuation of the medicine (see also Section 4.4 Special Warnings).

Psychiatric disorders

Disorientation, restlessness or agitation, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

Renal and urinary disorders

Urinary retention

Respiratory, thoracic and mediastinal disorders

Bronchospasm, apnoea

Skin and subcutaneous tissue disorders

Urticaria, drug rash, angioedema, allergic skin reactions, fixed drug eruption

Vascular disorders

Hypertension

IV formulation only:

Blisters at the site of injection and pruritus, as well as sensation of heaviness, chills, agitation, flushing and hypotension have been reported.

Rapid IV administration can lead to symptoms similar to overdose.

10.  DATE OF (PARTIAL) REVISION OF TEXT

June 2010

 



Numerous changes to Valoid Injection SPC as noted below in bold:

 

1.             TRADE NAME OF THE MEDICINAL PRODUCT

 

Valoid Solution for Injection 50mg/ml

 

 

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 1ml ampoule contains 50mg cyclizine lactate

For a full list of excipients, see section 6.1

 

 

3.       PHARMACEUTICAL FORM

 

Solution for Injection (Injection).

Clear, colourless solution for injection

 

4.1.    Therapeutic Indications

 

Valoid is indicated for the prevention and treatment of nausea and vomiting, including:-

·        Motion sickness, when the oral route can not be used.

·        Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the post-operative period.

·        Vomiting associated with radiotherapy, especially for breast cancer since cyclizine does not elevate prolactin levels.

·        Valoid injection, by the intravenous route, is also indicated pre-operatively in patients undergoing emergency surgery in order to reduce the hazard of regurgitation and aspiration of gastric contents during induction of general anaesthesia.

 

Valoid may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance when the oral route can not be used.

 

4.2.       Posology and Method of Administration

 

Route of Administration: intramuscularly or intravenously

 

Adults

50mg intramuscularly or intravenously, which may be repeated up to three times a day.

 

When used intravenously Valoid should be injected slowly into the bloodstream with only minimal withdrawal of blood into the syringe.

 

For the prevention of postoperative nausea and vomiting, administer the first dose by slow intravenous injection 20 minutes before the anticipated end of surgery.

 

Cyclizine given intravenously, in half the recommended dose, increases the lower oesophageal sphincter tone and thereby reduces the hazard of regurgitation and aspiration of gastric contents if given to patients, undergoing emergency surgery, before induction of general anaesthesia.

 

Use in the elderly: There have been no specific studies of Valoid in the elderly.  Experience has indicated that normal adult dosage is appropriate.

 

4.3.       Contraindications

 

Valoid is contraindicated in individuals with known hypersensitivity to cyclizine.

 

4.4.    Special Warnings and Precautions for Use

 

As with other anticholinergic agents, Valoid may precipate incipient glaucoma and it It should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy. 

 

Cyclizine should be used with caution in patients with severe heart failure.  In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure.

 

Cyclizine should be avoided in porphyria.

 

There have been reports of abuse of cyclizine, either oral or intravenous for its euphoric or hallucinatory effects. The concomitant misuse of Valoid with large amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine may increase the toxicity of alcohol.

 

Isolated cases of transient paralysis have been reported in patients with underlying neuromuscular disease/epilepsy. Therefore caution should be applied when using cyclizine.

 

4.6.    Pregnancy and Lactation

 

In the absence of any definitive human data, the use of Valoid in pregnancy is not advised. 

 

It is not known whether cyclizine or its metabolite are excreted in human milk.

 

4.7.    Effects on Ability to Drive and Use Machines

 

Studies designed to detect drowsiness, did not reveal sedation in healthy adults who took a single oral therapeutic dose (50 mg) of cyclizine, sedation of short duration was reported by subjects receiving intravenous cyclizine. 

 

Patients should not drive or operate machinery until they have determined their own response.

 

Although there are no data available, patients should be cautioned that Valoid may have additive effects with alcohol and other central nervous system depressants, e.g. hypnotics and tranquilizers.

 

4.8.    Undesirable Effects

 

Blood and lymphatic system disorders

Agranulocytosis

 

Cardiac disorders

Tachycardia

 

Eye disorders

Blurred vision, oculogyration

 

Gastrointestinal system disorders

Dryness of the mouth, nose and throat, constipation

 

General disorders and administration site conditions

Asthenia, malaise

 

Hepatobiliary disorders

Hepatic dysfunction including hepatitis due to hypersensitivity.  Cholestatic jaundice and cholestatic hepatitis have occurred in association with cyclizine.

 

Immune system disorders

Hypersensitivity reactions, including anaphylaxis, hypersensitivity hepatitis have occurred

 

Musculoskeletal and connective tissue disorders

Twitching, muscle spasms

 

 

Nervous system disorders

Effects on the central nervous system have been reported with cyclizine these include somnolence, headache, dystonia (sometimes associated with transient episodes of loss of consciousness and/or responsiveness to stimuli), dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.

 

Psychiatric disorders

Disorientation, restlessness, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

 

Renal and urinary disorders

Urinary retention

 

Respiratory, thoracic and mediastinal disorders

Bronchospasm, apnoea

 

Skin and subcutaneous tissue disorders

Urticaria, drug rash, angioedema, allergic skin reactions, fixed drug eruption

 

Vascular disorders

Hypertension

 

IV formulation only:

Blisters at the site of injection and pruritus, as well as sensation of heaviness, chills, agitation and hypotension have been reported.

 

4.9.    Overdose

 

Symptoms: Symptoms of acute toxicity from Valoid cyclizine arise from peripheral anticholinergic effects and effects on the central nervous system. 

 

Peripheral anticholinergic symptoms include, dry mouth, nose and throat, blurred vision, tachycardia and urinary retention.   Central nervous system effects include drowsiness, dizziness, incoordination, ataxia, weakness, hyperexcitability, disorientation, impaired judgement, hallucinations, hyperkinesia, extrapyramidal motor disturbances, convulsions, hyperpyrexia and respiratory depression. 

 

An oral dose of 5 mg/kg is likely to be associated with at least one of the clinical symptoms stated above.  Younger children are more susceptible to convulsions.  The incidence of convulsions, in children less than five years, is about 60% when the oral dose ingested exceeds 40 mg/kg.

 

Treatment:  In the management of acute overdosage with Valoid gastric lavage and supportive measures for respiration and circulation should be performed if necessary.  Convulsions should be controlled in the usual way with parenteral anticonvulsant therapy.

 

 

5.1.    Pharmacodynamic Properties

 

ATC Code: R60AE03

 

Pharmacotherapeutic Group: Piperazine derivatives

 

Mode of action:

Cyclizine is a histamine H1 receptor antagonist of the piperazine class, which is characterised by a low incidence of drowsiness.  It possesses anticholinergic and antiemetic properties.  The exact mechanism by which cyclizine can prevent or suppress both nausea and vomiting from various causes is unknown.  Cyclizine increases lower oesophageal sphincter tone and reduces the sensitivity of the labyrinthine apparatus.  It may inhibit the part of the midbrain known collectively as the emetic centre.

 

Pharmacodynamics:  

Cyclizine produces its anti-emetic effect within two hours and lasts approximately four  hours.

 

5.2.    Pharmacokinetic Properties

 

In healthy adult volunteers the administration of a single oral dose of 50mg cyclizine resulted in the peak plasma concentration of approximately 70ng/mL occurring at about  two hours after drug administration.  The plasma elimination half-life was approximately 20 hours.

 

The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine.  Norcyclizine has little antihistaminic (H₁) activity compared to cyclizine and has a plasma elimination half-life of approximately 20 hours.

 

After a single dose of 50 mg cyclizine given to a single adult male volunteer, urine collected over the following 24 hours contained less than 1% of the total dose administered.

 

5.3.    Preclinical Safety Data

 

A.        Mutagenicity:

Cyclizine was not mutagenic in a full Ames test, including use of S9-microsomes but can nitrosate in vitro to form mutagenic products.

 

B.        Carcinogenicity:

No long-term studies have been conducted in animals to determine whether cyclizine has a potential for carcinogenesis. However, long-term studies with cyclizine administered with nitrate have indicated no carcinogenicity.

 

C.        Teratogenicity:

Some animal studies are interpreted as indicating that cyclizine may be teratogenic.  The relevance of these studies to the human situation is not known.

 

D.        Fertility:

In a study involving prolonged administration of cyclizine to male and female rats there was no evidence of impaired fertility after continuous treatment for 90-100 days.  There is no experience of the effect of Valoid on human fertility.

 

 

6.2.    Incompatibilities

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

 

6.4.    Special Precautions for Storage

 

Do not store above 25°C.

Keep the ampoule in the outer carton.

 

6.5.    Nature and Contents of Container

 

1 ml neutral glass ampoules.  Five ampoules in a carton.

 

 

6.6.         Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

For single use only. Discard any unused contents.

 

 

10 DATE OF (PARTIAL) REVISION OF TEXT

 

April 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



Numerous changes to Valoid Injection SPC as noted below in bold:

 

1.             TRADE NAME OF THE MEDICINAL PRODUCT

 

Valoid Solution for Injection 50mg/ml

 

 

2.             QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 1ml ampoule contains 50mg cyclizine lactate

For a full list of excipients, see section 6.1

 

 

3.       PHARMACEUTICAL FORM

 

Solution for Injection (Injection).

Clear, colourless solution for injection

 

4.1.    Therapeutic Indications

 

Valoid is indicated for the prevention and treatment of nausea and vomiting, including:-

·        Motion sickness, when the oral route can not be used.

·        Nausea and vomiting caused by narcotic analgesics and by general anaesthetics in the post-operative period.

·        Vomiting associated with radiotherapy, especially for breast cancer since cyclizine does not elevate prolactin levels.

·        Valoid injection, by the intravenous route, is also indicated pre-operatively in patients undergoing emergency surgery in order to reduce the hazard of regurgitation and aspiration of gastric contents during induction of general anaesthesia.

 

Valoid may be of value in relieving vomiting and attacks of vertigo associated with Meniere's disease and other forms of vestibular disturbance when the oral route can not be used.

 

4.2.       Posology and Method of Administration

 

Route of Administration: intramuscularly or intravenously

 

Adults

50mg intramuscularly or intravenously, which may be repeated up to three times a day.

 

When used intravenously Valoid should be injected slowly into the bloodstream with only minimal withdrawal of blood into the syringe.

 

For the prevention of postoperative nausea and vomiting, administer the first dose by slow intravenous injection 20 minutes before the anticipated end of surgery.

 

Cyclizine given intravenously, in half the recommended dose, increases the lower oesophageal sphincter tone and thereby reduces the hazard of regurgitation and aspiration of gastric contents if given to patients, undergoing emergency surgery, before induction of general anaesthesia.

 

Use in the elderly: There have been no specific studies of Valoid in the elderly.  Experience has indicated that normal adult dosage is appropriate.

 

4.3.       Contraindications

 

Valoid is contraindicated in individuals with known hypersensitivity to cyclizine.

 

4.4.    Special Warnings and Precautions for Use

 

As with other anticholinergic agents, Valoid may precipate incipient glaucoma and it It should be used with caution and appropriate monitoring in patients with glaucoma, obstructive disease of the gastrointestinal tract, hepatic disease, epilepsy and in males with possible prostatic hypertrophy. 

 

Cyclizine should be used with caution in patients with severe heart failure.  In such patients, cyclizine may cause a fall in cardiac output associated with increases in heart rate, mean arterial pressure and pulmonary wedge pressure.

 

Cyclizine should be avoided in porphyria.

 

There have been reports of abuse of cyclizine, either oral or intravenous for its euphoric or hallucinatory effects. The concomitant misuse of Valoid with large amounts of alcohol is particularly dangerous, since the antiemetic effect of cyclizine may increase the toxicity of alcohol.

 

Isolated cases of transient paralysis have been reported in patients with underlying neuromuscular disease/epilepsy. Therefore caution should be applied when using cyclizine.

 

4.6.    Pregnancy and Lactation

 

In the absence of any definitive human data, the use of Valoid in pregnancy is not advised. 

 

It is not known whether cyclizine or its metabolite are excreted in human milk.

 

4.7.    Effects on Ability to Drive and Use Machines

 

Studies designed to detect drowsiness, did not reveal sedation in healthy adults who took a single oral therapeutic dose (50 mg) of cyclizine, sedation of short duration was reported by subjects receiving intravenous cyclizine. 

 

Patients should not drive or operate machinery until they have determined their own response.

 

Although there are no data available, patients should be cautioned that Valoid may have additive effects with alcohol and other central nervous system depressants, e.g. hypnotics and tranquilizers.

 

4.8.    Undesirable Effects

 

Blood and lymphatic system disorders

Agranulocytosis

 

Cardiac disorders

Tachycardia

 

Eye disorders

Blurred vision, oculogyration

 

Gastrointestinal system disorders

Dryness of the mouth, nose and throat, constipation

 

General disorders and administration site conditions

Asthenia, malaise

 

Hepatobiliary disorders

Hepatic dysfunction including hepatitis due to hypersensitivity.  Cholestatic jaundice and cholestatic hepatitis have occurred in association with cyclizine.

 

Immune system disorders

Hypersensitivity reactions, including anaphylaxis, hypersensitivity hepatitis have occurred

 

Musculoskeletal and connective tissue disorders

Twitching, muscle spasms

 

 

Nervous system disorders

Effects on the central nervous system have been reported with cyclizine these include somnolence, headache, dystonia (sometimes associated with transient episodes of loss of consciousness and/or responsiveness to stimuli), dyskinesia, extrapyramidal motor disturbances, tremor, convulsions, dizziness, decreased consciousness, transient speech disorders, paraesthesia and generalised chorea.

 

Psychiatric disorders

Disorientation, restlessness, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

 

Renal and urinary disorders

Urinary retention

 

Respiratory, thoracic and mediastinal disorders

Bronchospasm, apnoea

 

Skin and subcutaneous tissue disorders

Urticaria, drug rash, angioedema, allergic skin reactions, fixed drug eruption

 

Vascular disorders

Hypertension

 

IV formulation only:

Blisters at the site of injection and pruritus, as well as sensation of heaviness, chills, agitation and hypotension have been reported.

 

4.9.    Overdose

 

Symptoms: Symptoms of acute toxicity from Valoid cyclizine arise from peripheral anticholinergic effects and effects on the central nervous system. 

 

Peripheral anticholinergic symptoms include, dry mouth, nose and throat, blurred vision, tachycardia and urinary retention.   Central nervous system effects include drowsiness, dizziness, incoordination, ataxia, weakness, hyperexcitability, disorientation, impaired judgement, hallucinations, hyperkinesia, extrapyramidal motor disturbances, convulsions, hyperpyrexia and respiratory depression. 

 

An oral dose of 5 mg/kg is likely to be associated with at least one of the clinical symptoms stated above.  Younger children are more susceptible to convulsions.  The incidence of convulsions, in children less than five years, is about 60% when the oral dose ingested exceeds 40 mg/kg.

 

Treatment:  In the management of acute overdosage with Valoid gastric lavage and supportive measures for respiration and circulation should be performed if necessary.  Convulsions should be controlled in the usual way with parenteral anticonvulsant therapy.

 

 

5.1.    Pharmacodynamic Properties

 

ATC Code: R60AE03

 

Pharmacotherapeutic Group: Piperazine derivatives

 

Mode of action:

Cyclizine is a histamine H1 receptor antagonist of the piperazine class, which is characterised by a low incidence of drowsiness.  It possesses anticholinergic and antiemetic properties.  The exact mechanism by which cyclizine can prevent or suppress both nausea and vomiting from various causes is unknown.  Cyclizine increases lower oesophageal sphincter tone and reduces the sensitivity of the labyrinthine apparatus.  It may inhibit the part of the midbrain known collectively as the emetic centre.

 

Pharmacodynamics:  

Cyclizine produces its anti-emetic effect within two hours and lasts approximately four  hours.

 

5.2.    Pharmacokinetic Properties

 

In healthy adult volunteers the administration of a single oral dose of 50mg cyclizine resulted in the peak plasma concentration of approximately 70ng/mL occurring at about  two hours after drug administration.  The plasma elimination half-life was approximately 20 hours.

 

The N-demethylated derivative, norcyclizine, has been identified as a metabolite of cyclizine.  Norcyclizine has little antihistaminic (H₁) activity compared to cyclizine and has a plasma elimination half-life of approximately 20 hours.

 

After a single dose of 50 mg cyclizine given to a single adult male volunteer, urine collected over the following 24 hours contained less than 1% of the total dose administered.

 

5.3.    Preclinical Safety Data

 

A.        Mutagenicity:

Cyclizine was not mutagenic in a full Ames test, including use of S9-microsomes but can nitrosate in vitro to form mutagenic products.

 

B.        Carcinogenicity:

No long-term studies have been conducted in animals to determine whether cyclizine has a potential for carcinogenesis. However, long-term studies with cyclizine administered with nitrate have indicated no carcinogenicity.

 

C.        Teratogenicity:

Some animal studies are interpreted as indicating that cyclizine may be teratogenic.  The relevance of these studies to the human situation is not known.

 

D.        Fertility:

In a study involving prolonged administration of cyclizine to male and female rats there was no evidence of impaired fertility after continuous treatment for 90-100 days.  There is no experience of the effect of Valoid on human fertility.

 

 

6.2.    Incompatibilities

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

 

6.4.    Special Precautions for Storage

 

Do not store above 25°C.

Keep the ampoule in the outer carton.

 

6.5.    Nature and Contents of Container

 

1 ml neutral glass ampoules.  Five ampoules in a carton.

 

 

6.6.         Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

For single use only. Discard any unused contents.

 

 

10 DATE OF (PARTIAL) REVISION OF TEXT

 

April 2009

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note: Additional text is shown in red, removed text is shown with strikethrough

 

2.            QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 1ml ampoule contains 50mg cyclizine lactate.

 

For excipients, see 6.1

 

3.            PHARMACEUTICAL FORM

 

Solution for injection.

 

Clear, colourless solution for injection.

 

4.8.            Undesirable effects

 

Drowsiness, dryness of the mouth, nose and throat, blurred vision, tachycardia, urinary retention, constipation, restlessness, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

 

Following oral administration, single case reports have been documented of fixed drug eruption, generalised chorea, hypersensitivity hepatitis and agranulocytosis.  A single case of anaphylaxis has been recorded following intravenous administration of cyclizine co-administered with propanidid in the same syringe.  An increase in excitatory phenomena (tremor and muscle movements) has been reported when cyclizine has been given before propanidid and methohexitone anaesthesia.

 

Other Central Nervous effects which have been reported rarely include dystonia, dyskinesia, extrapyrimidal motor disturbances, tremor, twitching, muscle spasms, convulsions, disorientation, dizziness, decreased consciousness, paraesthesia and transient speech disorders.

 

Rare reports of cholestatic hepatitis and hypersensitivity reactions, including anaphylaxis, angiodema, allergic skin reactions and bronchospasm, have been reported in association with cyclizine.  There have also been a few reports of fixed drug eruption, apnoea, generalized chorea, hypersensitivity hepatitis, hepatic dysfunction and agranulocytosis.

 

A single case of anaphylaxis has been recorded following intravenous administration of cyclizine co-administered with propanidid in the same syringe.

 

Injection site reactions including vein tracking, erythema, pain and thrombophlebitis have been reported rarely.

 

6.4.            Special precautions for storage

 

Do not store above 25°C. Protect from light.  Keep the ampoule in the outer carton.

 

6.6.            Instructions for use, handling and disposal

 

None No special requirements.

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

1st April 1979/ 1st April 1999 2004

 

10.       DATE OF REVISION OF THE TEXT

 

November 2005

 

 

 

Note: Additional text is shown in red, removed text is shown with strikethrough

 

2.            QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each 1ml ampoule contains 50mg cyclizine lactate.

 

For excipients, see 6.1

 

3.            PHARMACEUTICAL FORM

 

Solution for injection.

 

Clear, colourless solution for injection.

 

4.8.            Undesirable effects

 

Drowsiness, dryness of the mouth, nose and throat, blurred vision, tachycardia, urinary retention, constipation, restlessness, nervousness, insomnia and auditory and visual hallucinations have been reported, particularly when dosage recommendations have been exceeded.

 

Following oral administration, single case reports have been documented of fixed drug eruption, generalised chorea, hypersensitivity hepatitis and agranulocytosis.  A single case of anaphylaxis has been recorded following intravenous administration of cyclizine co-administered with propanidid in the same syringe.  An increase in excitatory phenomena (tremor and muscle movements) has been reported when cyclizine has been given before propanidid and methohexitone anaesthesia.

 

Other Central Nervous effects which have been reported rarely include dystonia, dyskinesia, extrapyrimidal motor disturbances, tremor, twitching, muscle spasms, convulsions, disorientation, dizziness, decreased consciousness, paraesthesia and transient speech disorders.

 

Rare reports of cholestatic hepatitis and hypersensitivity reactions, including anaphylaxis, angiodema, allergic skin reactions and bronchospasm, have been reported in association with cyclizine.  There have also been a few reports of fixed drug eruption, apnoea, generalized chorea, hypersensitivity hepatitis, hepatic dysfunction and agranulocytosis.

 

A single case of anaphylaxis has been recorded following intravenous administration of cyclizine co-administered with propanidid in the same syringe.

 

Injection site reactions including vein tracking, erythema, pain and thrombophlebitis have been reported rarely.

 

6.4.            Special precautions for storage

 

Do not store above 25°C. Protect from light.  Keep the ampoule in the outer carton.

 

6.6.            Instructions for use, handling and disposal

 

None No special requirements.

 

9.         DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

 

1st April 1979/ 1st April 1999 2004

 

10.       DATE OF REVISION OF THE TEXT

 

November 2005