Drugs List

Therapeutic Indications

Uses

Relief of chronic severe pain

Administration

For intrathecal use only.

For administration as a continuous intrathecal infusion via an intrathecal catheter, using an external or internally implanted mechanical infusion pump.

Internal systems are recommended when administering ziconotide for prolonged periods due to the risk of meningitis secondary to catheterisation of the intrathecal space.

External catheters should only be used when an internal system cannot be implanted.

When low dose of ziconotide are required, dilute before use with preservative-free sodium chloride 0.9% solution for injection

Contraindications

Children under 18 years
Concurrent intrathecal chemotherapy

Precautions and Warnings

Breastfeeding
Depression
Hepatic impairment
Pregnancy
Renal impairment

Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be administered only by an experienced intrathecal clinician
Monitor and discontinue if appropriate if psychiatric or CNS problems occur
Monitor patients with a history of depression and/or suicide attempts
Monitor serum creatine periodically
Remain alert to possible coincidental meningitis
Discontinue if myopathy is suspected
Discontinue if creatine kinase concentration increases significantly
Discontinue immediately if rhabdomyolysis occurs
Discontinue treatment in patients with depressed levels of consciousness

Pregnancy and Lactation

Pregnancy

There are no adequate data from the use of ziconotide in pregnant women.

There have been reproductive studies conducted in rats and rabbits. Ziconotide caused embryo death in pregnant rats given continuous intravenous (IV) infusions about 700 times higher than the expected plasma exposure resulting from the maximum recommended human daily intrathecal dose. There were no structural defects observed in rats and rabbits given continuous IV infusions during organogenesis that were up to about 26,000 and 940 times higher, respectively, that the expected plasma exposure resulting from the maximum recommended human dose. It is not known whether ziconotide crosses the human placenta, its molecular weight and the very low plasma concentrations suggest that little if any drug will reach the embryo. However, the potential risk in humans is unknown due to the lack of adequate data.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated due to the lack of information

At the time of writing there are no reports describing the use of ziconotide during human lactation. Although excretion into milk is possible, only small, probably clinically insignificant amounts of ziconotide appear in the plasma during intrathecal infusions. Therefore ziconotide should not be administered to breastfeeding women unless clearly necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Acute renal failure
Aggression
Agitation
Amnesia
Anaphylactic reaction
Anorexia
Anxiety
Aphasia
Areflexia
Arthralgia
Asthenia
Ataxia
Atrial fibrillation
Attention disturbances
Blurred vision
Burning sensation
Cerebrovascular accident
Cognitive impairment
Coma
Confusion
Constipation
Convulsions
Creatine phosphokinase increased
Decreased appetite
Delirium
Depression
Diarrhoea
Diplopia
Disorientation
Dizziness
Dream abnormalities
Dry mouth
Dysaesthesia
Dysarthria
Dysgeusia
Dyspepsia
Dyspnoea
Dysuria
ECG changes
Encephalopathy
Fatigue
Gait abnormality
Hallucinations
Headache
Hyporeflexia
Hypotension
Impaired co-ordination
Impaired consciousness
Impaired memory
Impairment of mental skills
Incoherence
Increase in AST level
Increased sweating
Insomnia
Irritability
Lability of affect
Lethargy
Loss of balance
Meningitis
Micturition disorders
Muscle spasm
Muscle twitch
Muscle weakness
Muscular cramps
Myalgia
Myositis
Nausea
Nervousness
Nystagmus
Orthostatic hypotension
Pain
Paraesthesia
Paranoia
Parosmia
Peripheral oedema
Photophobia
Postural dizziness
Pruritus
Psychotic reactions
Pyrexia
Rash
Respiratory distress syndrome
Rhabdomyolysis
Rigors
Sedation
Sensation of cold
Sepsis
Somnolence
Speech disturbances
Stupor
Suicidal tendencies
Swelling
Thought blocking
Tinnitus
Tremor
Upper abdominal pain
Vertigo
Vomiting
Weight loss

Presentation

Solution for intrathecal infusion containing ziconotide

Drugs List

Therapeutic Indications

Uses

Relief of chronic severe pain

Dosage

Treatment with ziconotide should only be undertaken by physicians experienced in intrathecal administration of medicinal products.

Adults

Elderly

Administration

For intrathecal use only.

For administration as a continuous intrathecal infusion via an intrathecal catheter, using an external or internally implanted mechanical infusion pump.

Internal systems are recommended when administering ziconotide for prolonged periods due to the risk of meningitis secondary to catheterisation of the intrathecal space.

External catheters should only be used when an internal system cannot be implanted.

When low dose of ziconotide are required, dilute before use with preservative-free sodium chloride 0.9% solution for injection

Contraindications

Children under 18 years
Concurrent intrathecal chemotherapy

Precautions and Warnings

Breastfeeding
Depression
Hepatic impairment
Pregnancy
Renal impairment

Patients at risk of suicide should be closely supervised
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be administered only by an experienced intrathecal clinician
Monitor and discontinue if appropriate if psychiatric or CNS problems occur
Monitor patients with a history of depression and/or suicide attempts
Monitor serum creatine periodically
Remain alert to possible coincidental meningitis
Discontinue if myopathy is suspected
Discontinue if creatine kinase concentration increases significantly
Discontinue immediately if rhabdomyolysis occurs
Discontinue treatment in patients with depressed levels of consciousness

Pregnancy and Lactation

Pregnancy

There are no adequate data from the use of ziconotide in pregnant women.

There have been reproductive studies conducted in rats and rabbits. Ziconotide caused embryo death in pregnant rats given continuous intravenous (IV) infusions about 700 times higher than the expected plasma exposure resulting from the maximum recommended human daily intrathecal dose. There were no structural defects observed in rats and rabbits given continuous IV infusions during organogenesis that were up to about 26,000 and 940 times higher, respectively, that the expected plasma exposure resulting from the maximum recommended human dose. It is not known whether ziconotide crosses the human placenta, its molecular weight and the very low plasma concentrations suggest that little if any drug will reach the embryo. However, the potential risk in humans is unknown due to the lack of adequate data.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated due to the lack of information

At the time of writing there are no reports describing the use of ziconotide during human lactation. Although excretion into milk is possible, only small, probably clinically insignificant amounts of ziconotide appear in the plasma during intrathecal infusions. Therefore ziconotide should not be administered to breastfeeding women unless clearly necessary.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Patients and caregivers should be alerted about the need to monitor for the emergence of depression, suicidal thoughts and behaviour and the need to seek medical advice immediately if they present.

Ziconotide may cause confusion, somnolence and other neurological adverse reactions, and so patients should be advised to exercise caution when driving or operating machinery.

Side Effects

Acute renal failure
Aggression
Agitation
Amnesia
Anaphylactic reaction
Anorexia
Anxiety
Aphasia
Areflexia
Arthralgia
Asthenia
Ataxia
Atrial fibrillation
Attention disturbances
Blurred vision
Burning sensation
Cerebrovascular accident
Cognitive impairment
Coma
Confusion
Constipation
Convulsions
Creatine phosphokinase increased
Decreased appetite
Delirium
Depression
Diarrhoea
Diplopia
Disorientation
Dizziness
Dream abnormalities
Dry mouth
Dysaesthesia
Dysarthria
Dysgeusia
Dyspepsia
Dyspnoea
Dysuria
ECG changes
Encephalopathy
Fatigue
Gait abnormality
Hallucinations
Headache
Hyporeflexia
Hypotension
Impaired co-ordination
Impaired consciousness
Impaired memory
Impairment of mental skills
Incoherence
Increase in AST level
Increased sweating
Insomnia
Irritability
Lability of affect
Lethargy
Loss of balance
Meningitis
Micturition disorders
Muscle spasm
Muscle twitch
Muscle weakness
Muscular cramps
Myalgia
Myositis
Nausea
Nervousness
Nystagmus
Orthostatic hypotension
Pain
Paraesthesia
Paranoia
Parosmia
Peripheral oedema
Photophobia
Postural dizziness
Pruritus
Psychotic reactions
Pyrexia
Rash
Respiratory distress syndrome
Rhabdomyolysis
Rigors
Sedation
Sensation of cold
Sepsis
Somnolence
Speech disturbances
Stupor
Suicidal tendencies
Swelling
Thought blocking
Tinnitus
Tremor
Upper abdominal pain
Vertigo
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2013

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Prialt solution for infusion. Eisai Ltd. Revised January 2017.