Peginterferon Beta-1A

Registered South African indications:

• Relapsing forms of multiple sclerosis

Contraindications
South African manufacturer recommendations

• Hypersensitivity to active ingredient or any of its excipients
• Hypersensitivity to natural or recombinant interferon beta
• Pregnancy
• Breastfeeding

International manufacturer recommendations

• Hypersensitivity to active ingredient or any of its excipients
• Hypersensitivity to natural or recombinant interferon beta
• Current severe depression and/or suicidal ideation

Cautions
South African manufacturer recommendations

• Severe hepatic impairment
• Elderly
• Pre-existing depression and suicidal ideation
• Pre-existing seizures disorders
• Myelosuppression
• Pre-existing significant cardiac disease:
  - Congestive heart failure
  - Coronary artery disease
  - Dysrhythmia

International manufacturer recommendations

• Pregnancy
• Severe renal impairment
  - Including those at higher risk of renal disease
• Severe hepatic impairment
• Elderly
• History of seizures
• Epilepsy
  - Those receiving treatment with anti-epileptics, particularly if epilepsy is not adequately controlled with anti-epileptics
• Previous depressive disorders
• Pre-existing significant cardiac disease
  - Congestive heart failure
  - Coronary artery disease
  - Arrhythmia
• History of thyroid dysfunction
• Myelosuppression
• Coadministration with agents with narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance (e.g. some classes of antiepileptics and antidepressants)

• Coadministration with other medicinal agents associated with hepatic injury

Forms avail. in SA and covered in this monograph: inj
Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations
Relapsing forms of multiple sclerosis
- To reduce the frequency of clinical exacerbations and to delay the progression of disability
Treatment initiation

Dose	Time*	Amount (μg)	Pen/Syringe
Dose 1	Day 1	63	Orange
Dose 2	Week 2	94	Blue
Dose 3	Week 4 (and thereafter)	125 (full dose)	Grey

*Dosed every 2 weeks
Maintenance dose

• SC: 125μg, every 2 weeks

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Sites for SC admin. include abdomen, arm and thigh. Sites should be rotated

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Pre-filled pen/syringes are for single use only, and should be discarded after use

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Missed dose: See additional prescribing points

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International manufacturer recommendations
Relapsing remitting multiple sclerosis
Treatment initiation SC route

Dose	Time*	Amount (μg)	Syringe label
Dose 1	Day 0	63	Orange
Dose 2	Day 14	94	Blue
Dose 3	Day 28	125 (full dose)	Grey

*Dosed every 2 weeks
Treatment initiation IM route

Dose	Time*	Amount (μg)	Titration clip
Dose 1	Day 0	63	Yellow
Dose 2	Day 14	94	Purple
Dose 3	Day 28	125 (full dose)	No clips needed

*Dosed every 2 weeks
Maintenance dose

• SC/IM: 125μg, every 2 weeks

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Switching between the SC and IM routes of administration and vice versa has not been studied. Based upon bioequivalence demonstrated between the two routes of administration it is not expected that dose titration will be required if switching between SC and IM, or vice versa

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Missed dose: See additional prescribing points

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Treatment should be initiated under supervision of a physician experienced in the treatment of multiple sclerosis

Not established for use in children below 18 years

Pregnancy
South African manufacturer recommendations

• Contraindicated
• Safety and efficacy in pregnant women have not been established
• Women who can become pregnant should use contraception while receiving peginterferon beta-1a

International manufacturer recommendations

• Caution
• A large amount of data (more than 1,000 pregnancy outcomes) from registries and post-marketing experience indicates no increased risk of major congenital anomalies after pre-conception exposure to interferon beta or such exposure during the first trimester of pregnancy. However, the duration of exposure during the first trimester is uncertain, because data were collected when interferon beta use was contraindicated during pregnancy, and treatment likely interrupted when pregnancy was detected and/or confirmed. Experience with exposure during the second and third trimester is very limited
• Based on animal data, there is a possibly increased risk for spontaneous abortion. The risk of spontaneous abortions in pregnant women exposed to interferon beta cannot adequately be evaluated based on the currently available data, but the data do not suggest an increased risk so far
• If clinically needed, the use of peginterferon beta-1a may be considered during pregnancy

Breastfeeding
South African manufacturer recommendations

• Contraindicated 
• It is not known if peginterferon beta-1a is secreted in human milk. Mothers should not breastfeed their infants while on peginterferon beta-1a

International manufacturer recommendations

• Compatible 
• It is not known whether peginterferon beta-1a is secreted in human milk. Limited information available on the transfer of interferon beta-1a into breast milk, together with the chemical/physiological characteristics of interferon beta, suggests that levels of interferon beta-1a excreted in human milk are negligible. No harmful effects on the breastfed newborn/infant are anticipated. Peginterferon beta-1a can be used during breastfeeding

Fertility 
South African manufacturer recommendations

• No information available

International manufacturer recommendations

• No data on the effects of peginterferon beta-1a on human fertility. In animals, anovulatory effects were observed at very high doses. No information is available on the effects of peginterferon beta-1a on male fertility in animals

Renal Impairment
South African manufacturer recommendations

• No dose adjustment recommended 

International manufacturer recommendations

• Mild to moderate: No dose adjustment recommended 
• Severe: Caution; no dose adjustment recommended 

Hepatic Impairment
South African manufacturer recommendations

• Mild to moderate: No dose adjustment recommended 
• Severe: Caution; no dose adjustment recommended 
  Patients should be monitored for signs and symptoms of hepatic injury and caution exercised when peginterferon beta-1a is coadministered with other agents associated with the hepatic injury

International manufacturer recommendations

• Caution; no information available 

Elderly

• Caution; no information available 

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Seizures
• Depression
• Asthenia

Respiratory Disorders

• Pulmonary arterial hypertension

Gastrointestinal Disorders

• Nausea and vomiting

Hepatobiliary Disorders

• Elevated bilirubin
• Increased alanine aminotransferase
• Increased aspartate aminotransferase
• Increased gamma-glutamyltransferase

Genitourinary Disorders

• Nephrotic syndrome
• Glomerulosclerosis

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Musculoskeletal pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Pruritus
• Urticaria
• Injection site reactions
  - Erythema
  - Pain
  - Pruritus
  - Inflammation
  - Haematoma
  - Swelling
  - Oedema
  - Rash
  - Warmth
  - Discolouration
  - Necrosis

Immune, Blood and Lymphatic System Disorders

• Angioedema
• Hypersensitivity
• Anaphylaxis
• Thrombocytopenia
• Thrombotic microangiopathy
• Thrombotic thrombocytopenic purpura
• Haemolytic uraemic syndrome
• Pyrexia
• Chills
• Influenza-like illness
• Decreased white blood cell count 
• Decreased haemoglobin
• Increased body temperature
• Decreased platelet count

Other

• Pain

No significant interactions

• Full blood count
• Platelets
• Hepatic function

Additional observations

• Signs and symptoms of
  - Hepatic injury
  - Thrombotic microangiopathy (e.g. new-onset hypertension, thrombocytopenia, renal impairment)
  - Injection-site reactions
  - Hypersensitivity
  - Infections
  - Bleeding
  - New onset autoimmune disorders
  - Psychiatric disorders (including depression and/or suicidal ideation)
  - New onset/worsening cardiovascular disease
  - Oedema
  - Proteinuria
  - Impaired renal function

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Dose titration at initiation

• Dose titration at the initiation of treatment may help to ameliorate flu-like symptoms that can occur at treatment initiation with interferons. Prophylactic and concurrent use of anti-inflammatory, analgesic and/or antipyretic treatments may prevent or ameliorate flu-like symptoms sometimes experienced during interferon treatment

Missed dose
South African manufacturer recommendations

• If a dose is missed, it should be taken as soon as patient remembers, however, two doses should not be taken within 7 days of each other

International manufacturer recommendations

• If a dose is missed, it should be administered as soon as possible
• If ≥7 days to the next planned dose: Patients should administer their missed dose immediately. Treatment can then continue with the next scheduled dose as planned
• If <7 days to the next planned dose: Patients should begin a new 2 week dosing schedule starting from when they administer their missed dose. Two doses should not be administered within 7 days of each other

A definitive mechanism of action of peginterferon beta-1a in multiple sclerosis (MS) is not known. Peginterferon beta-1a binds to the type I interferon receptor on the surface of cells and elicits a cascade of intracellular events leading to the regulation of interferon-responsive gene expression. Biological effects that may be mediated by peginterferon beta-1a include up-regulation of anti-inflammatory cytokines (e.g. IL-4, IL-10, IL-27), down-regulation of pro-inflammatory cytokines (e.g. IL-2, IL-12, IFN-γ, TNF-α) and inhibiting the migration of activated T cells across the blood brain barrier; however additional mechanisms may be involved. Whether the mechanism of action of peginterferon beta-1a in MS is mediated by the same pathway(s) as the biological effects described above is not known because the pathophysiology of MS is only partially understood.

Injection (per 0.5ml) 63μg & 94μg

• Plegridy starter pack (Acino Pharma)

Injection (per 0.5ml) 125μg

• Plegridy 125μg (Acino Pharma)