Drugs List

Therapeutic Indications

Uses

Stable angina pectoris: Adjunctive treatment

Use in combination for the symptomatic treatment of patients with stable angina pectoris who are intolerant to or not adequately controlled by first line antianginal treatments (such as beta-blockers and/or calcium antagonists).

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Long QT syndrome
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Weight below 60kg
CYP2D6 poor metaboliser genotype
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Lactose intolerance
Mild hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Renal impairment - creatinine clearance 30-80ml/minute

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain lactose
Some formulations contain tartrazine
Consider monitoring ECG in patients at risk of QT prolongation
Monitor renal function regularly
Monitor serum electrolytes
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Remind patient of importance of carrying Alert Card with them at all times

If ranolazine is used in a patient with a combination of risk factors frequent monitoring of side effects and reduced dose are recommended. Discontinuation of treatment may be required.

Patient who are known to have low CYP2D6 metabolising capacity may be treated with ranolazine but caution should be exercised when they have a combination of several risk factors.

Pregnancy and Lactation

Pregnancy

Ranolazine is contraindicated in pregnancy.

At the time of writing, there is no published experience concerning exposed human pregnancies and their outcomes. The manufacturer reports that there are insufficient animal studies with respect to the effects on pregnancy and embryo development. As the potential risk is unknown the use of ranolazine is contraindicated during pregnancy, and other antianginal agents with more data on their use during pregnancy should be considered first.

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

Ranolazine is contraindicated in breastfeeding.

It is unknown whether ranolazine is excreted into human breast milk. Therefore, ranolazine should not be used by nursing mothers.

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

Abdominal discomfort
Abdominal pain
Acute renal failure
Allergic dermatitis
Amnesia
Angioedema
Anorexia
Anxiety
Asthenia
Blood urea increased
Blurred vision
Chromaturia
Cold sweat
Confusion
Constipation
Cough
Decreased appetite
Dehydration
Diplopia
Disorientation
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Epistaxis
Erectile dysfunction
Erosive duodenitis
Fatigue
Flatulence
Gait abnormality
Haematuria
Hallucinations
Headache
Hearing disturbances
Hot flushes
Hypoaesthesia
Hyponatraemia
Hypotension
Impaired co-ordination
Impaired consciousness
Increased platelet count
Increased sweating
Increases in hepatic enzymes
Insomnia
Joint swelling
Lethargy
Leucocytosis
Muscle weakness
Muscular cramps
Nausea
Oral hypoaesthesia
Orthostatic hypotension
Painful extremities
Pancreatitis
Paraesthesia
Parosmia
Peripheral coldness
Peripheral oedema
Postural dizziness
Prolongation of QT interval
Pruritus
Rash
Serum creatinine increased
Somnolence
Syncope
Throat tightness
Tinnitus
Tremor
Unconsciousness
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Weight loss

Presentation

Prolonged release oral formulation of ranolazine

Drugs List

Therapeutic Indications

Uses

Stable angina pectoris: Adjunctive treatment

Use in combination for the symptomatic treatment of patients with stable angina pectoris who are intolerant to or not adequately controlled by first line antianginal treatments (such as beta-blockers and/or calcium antagonists).

Dosage

Adults

Elderly

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Long QT syndrome
Moderate hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Torsade de pointes

Precautions and Warnings

Elderly
Family history of long QT syndrome
Weight below 60kg
CYP2D6 poor metaboliser genotype
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
History of torsade de pointes
Lactose intolerance
Mild hepatic impairment
New York Heart Association class III failure
New York Heart Association class IV failure
Renal impairment - creatinine clearance 30-80ml/minute

Correct electrolyte disorders before treatment
Advise ability to drive/operate machinery may be affected by side effects
Some formulations contain lactose
Some formulations contain tartrazine
Consider monitoring ECG in patients at risk of QT prolongation
Monitor renal function regularly
Monitor serum electrolytes
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Remind patient of importance of carrying Alert Card with them at all times

If ranolazine is used in a patient with a combination of risk factors frequent monitoring of side effects and reduced dose are recommended. Discontinuation of treatment may be required.

Patient who are known to have low CYP2D6 metabolising capacity may be treated with ranolazine but caution should be exercised when they have a combination of several risk factors.

Pregnancy and Lactation

Pregnancy

Ranolazine is contraindicated in pregnancy.

At the time of writing, there is no published experience concerning exposed human pregnancies and their outcomes. The manufacturer reports that there are insufficient animal studies with respect to the effects on pregnancy and embryo development. As the potential risk is unknown the use of ranolazine is contraindicated during pregnancy, and other antianginal agents with more data on their use during pregnancy should be considered first.

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

Ranolazine is contraindicated in breastfeeding.

It is unknown whether ranolazine is excreted into human breast milk. Therefore, ranolazine should not be used by nursing mothers.

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

Abdominal discomfort
Abdominal pain
Acute renal failure
Allergic dermatitis
Amnesia
Angioedema
Anorexia
Anxiety
Asthenia
Blood urea increased
Blurred vision
Chromaturia
Cold sweat
Confusion
Constipation
Cough
Decreased appetite
Dehydration
Diplopia
Disorientation
Dizziness
Dry mouth
Dyspepsia
Dyspnoea
Dysuria
Epistaxis
Erectile dysfunction
Erosive duodenitis
Fatigue
Flatulence
Gait abnormality
Haematuria
Hallucinations
Headache
Hearing disturbances
Hot flushes
Hypoaesthesia
Hyponatraemia
Hypotension
Impaired co-ordination
Impaired consciousness
Increased platelet count
Increased sweating
Increases in hepatic enzymes
Insomnia
Joint swelling
Lethargy
Leucocytosis
Muscle weakness
Muscular cramps
Nausea
Oral hypoaesthesia
Orthostatic hypotension
Painful extremities
Pancreatitis
Paraesthesia
Parosmia
Peripheral coldness
Peripheral oedema
Postural dizziness
Prolongation of QT interval
Pruritus
Rash
Serum creatinine increased
Somnolence
Syncope
Throat tightness
Tinnitus
Tremor
Unconsciousness
Urinary retention
Urticaria
Vertigo
Visual disturbances
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: July 2016

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press Accessed on 5 July 2016.

Summary of Product Characteristics: Ranexa prolonged-release tablets. A.Menarini Farmaceutica Internazionale SRL. Revised November 2015.