Indications and Dosage

Peripheral and Central Neuropathic Pain

• By Mouth (Adults):

• • Initial Dose: 150 mg daily, divided into 2-3 doses.
  • Adjustments: Increase to 300 mg daily in 2-3 divided doses after 3-7 days if necessary.
  • Further Adjustments: If needed, increase to 600 mg daily in 2-3 divided doses after 7 days.

Adjunctive Therapy for Focal Seizures

• By Mouth (Adults):

• • Initial Dose: 25 mg twice daily.
  • Adjustments: Increase in steps of 50 mg daily every 7 days.
  • Stabilization: Increase to 300 mg daily in 2-3 divided doses for 7 days.
  • Further Adjustments: If necessary, increase up to 600 mg daily in 2-3 divided doses.

Generalised Anxiety Disorder

• By Mouth (Adults):

• • Initial Dose: 150 mg daily, divided into 2-3 doses.
  • Adjustments: Increase in steps of 150 mg daily every 7 days if required.
  • Maximum Dose: Increase up to 600 mg daily in 2-3 divided doses if necessary.

General Notes:

• Dose adjustments should be tailored based on patient response and tolerability.
• Monitor for efficacy and any potential side effects during dose escalation.
• Pregabalin should be administered in divided doses, with a specific focus on gradual increases to minimize side effects and optimize therapeutic outcomes.

Important Safety Information for Pregabalin (Lyrica®)

MHRA/CHM Advice on Antiepileptics:

1. Risk of Suicidal Thoughts and Behavior (August 2008):

1. • There is an associated risk of suicidal thoughts and behavior with antiepileptic drugs.

1. Switching Between Different Manufacturers’ Products (November 2017):

1. • Updated advice suggests caution when switching between different manufacturers’ products due to variations in clinical effects.

1. Antiepileptic Drugs in Pregnancy (January 2021):

1. • Following a comprehensive safety review, updated advice on the use of antiepileptic drugs during pregnancy is provided.

Specific Advice for Pregabalin:

1. Risk of Abuse and Dependence (April 2019):

1. • Pregabalin has been reclassified as a Class C controlled substance and is now Schedule 3. It is exempt from safe custody requirements.
   • Healthcare providers should screen patients for a history of drug abuse before prescribing and monitor for signs of abuse and dependence.
   • Patients should be warned about the potentially fatal risks of interactions between pregabalin and alcohol, and with other CNS depressants, particularly opioids.

1. Risks During Pregnancy (April 2022):

1. • Studies indicate a slightly increased risk of major congenital malformations in the unborn child from first-trimester use, compared to those taking lamotrigine, duloxetine, or no antiepileptic drugs.
   • Advice for healthcare professionals:

1. • • Counsel patients on potential risks to an unborn baby and the need for effective contraception during treatment.
     • Avoid use during pregnancy unless necessary, where the benefits outweigh the risks.
     • Advise pregnant women or those planning to become pregnant to discuss their treatment options with their healthcare provider.

1. Reports of Severe Respiratory Depression (February 2021):

1. • Reports have identified cases of severe respiratory depression, sometimes without concurrent opioid use.
   • Consider dose adjustments or changes in dosing regimen for patients at risk of respiratory depression, including those with compromised respiratory function, neurological disease, renal impairment, or those taking other CNS depressants.
   • Advise patients, especially those over 65, to seek immediate medical help if they experience any breathing difficulties or changes.

Cautions

• Respiratory Depression: Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, those using CNS depressants, and the elderly are at higher risk of severe respiratory depression. Dose adjustments may be necessary.
• Seizure Exacerbation: Pregabalin may exacerbate seizures in patients with specific seizure disorders such as absence or myoclonic seizures, Dravet syndrome, Lennox-Gastaut syndrome, and myoclonic-atonic seizures.

Side Effects

• Common/Very Common: Abdominal distension, abnormal appetite, asthenia, cervical spasm, impaired concentration, confusion, constipation, diarrhea, dizziness, drowsiness, dry mouth, abnormal gait, gastrointestinal disorders, headache, increased risk of infection, joint disorders, memory loss, altered mood, movement disorders, muscle complaints, nausea, edema, pain, abnormal sensation, sexual dysfunction, sleep disorders, speech impairment, vertigo, vision disorders, vomiting, weight changes.
• Uncommon: Aggression, anxiety, arrhythmias, atrioventricular block, breast abnormalities, chest tightness, chills, impaired consciousness, cough, depression, dry eyes, dyspnea, epistaxis, eye discomfort, eye disorders, eye inflammation, fever, hallucinations, hyperacusis, hypertension, hypoglycemia, hypotension, malaise, menstrual cycle irregularities, nasal complaints, neutropenia, oral disorders, peripheral coldness, psychiatric disorders, decreased reflexes, skin reactions, snoring, sweat changes, syncope, taste loss, thirst, urinary disorders, vasodilation.
• Rare/Very Rare: Altered smell sensation, ascites, dysgraphia, dysphagia, gynecomastia, hepatic disorders, pancreatitis, pulmonary edema, QT interval prolongation, renal impairment, rhabdomyolysis, Stevens-Johnson syndrome, throat tightness.
• Frequency Not Known: Drug use disorders, encephalopathy, respiratory depression, suicidal behaviors, withdrawal syndrome.

Special Considerations

• Pregnancy: Avoid unless the benefit clearly outweighs potential risk. Use in the first trimester is associated with a slightly increased risk of major birth defects.
• Breastfeeding: Weigh benefits against risks.
• Renal Impairment: Dose adjustments are necessary based on creatinine clearance.

• • Creatinine clearance 30-60 mL/minute: Initially 75 mg daily, maximum 300 mg daily.
  • Creatinine clearance 15-30 mL/minute: Initially 25-50 mg daily, maximum 150 mg daily.
  • Creatinine clearance less than 15 mL/minute: Initially 25 mg once daily, maximum 75 mg once daily.

Monitoring and Treatment Cessation

• Monitoring for Abuse: Regular monitoring for signs of Pregabalin misuse is advised.
• Avoid Abrupt Withdrawal: Gradually taper dose over at least one week to prevent withdrawal symptoms.

Patient and Carer Advice

• Driving and Performing Skilled Tasks: Advise on the potential effects like dizziness or vision disorders that can impair the ability to drive or perform skilled tasks.

Medicinal Forms

Tablets

• Pregabalin Tablets (Non-proprietary):

• • Available in various strengths: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg.

Oral Solution

• Pregabalin Oral Solution (Non-proprietary):

• • 20 mg per 1 ml, available sugar-free.

• Lyrica Oral Solution (Viatris UK Healthcare Ltd):

• • 20 mg per 1 ml, sugar-free.

Capsules

• Pregabalin Capsules (Non-proprietary):

• • Available in several strengths: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg.

• Lyrica Capsules (Viatris UK Healthcare Ltd):

• • Available in several strengths: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg.

• Alzain Capsules (Dr Reddy’s Laboratories (UK) Ltd):

• • Available in various strengths: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg.

• Axalid Capsules (Kent Pharma (UK) Ltd):

• • Available in strengths ranging from 25 mg to 300 mg.