Peginterferon alfa-2a is a medication used in the treatment of certain viral infections, particularly hepatitis B and C. It belongs to a class of drugs known as interferons, which are proteins produced naturally by the body in response to infections.

The "peg" in peginterferon refers to polyethylene glycol, a substance added to the medication to prolong its effects in the body. Pegylation helps slow down the clearance of the drug from the bloodstream, allowing for less frequent dosing.

Peginterferon alfa-2a works by boosting the body's immune response to viruses, helping to suppress viral replication and potentially clearing the infection over time. It is typically used in combination with other antiviral medications, such as ribavirin, for the treatment of hepatitis C.

Pegasys (Peginterferon Alfa-2a) is prepared by recombinant DNA technology that is used to treat patients with chronic hepatitis B and chronic hepatitis C infections.

Peginterferon Alfa-2a Uses:

• Chronic hepatitis B:
  • Treatment of adults with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B virus (HBV) infection with compensated liver disease and evidence of viral replication and liver inflammation.
  • Treatment of pediatric patients 3 years and older with HBeAg-positive chronic HBV infection who are non-cirrhotic and have evidence of viral replication and increased serum alanine aminotransferase.
• Chronic hepatitis C:
  • Combination therapy: Treatment of adults with chronic hepatitis C (CHC) with compensated liver disease as part of a combination regiment with other hepatitis C virus (HCV) antiviral drugs.
  • Treatment of pediatric patients 5 years and older with CHC and compensated liver disease combined with ribavirin.
  • Note:
    • Current AASLD/IDSA guidelines do not recommend the use of interferon products.
    • Peginterferon and ribavirin, typically combined with a direct-acting antiviral, remain in use for certain genotypes, especially in resource-limited settings where newer interferon-free regimens are not available.
  • Monotherapy (for patients having contraindications or who are who cannot tolerate other HCV antiviral drugs):
    • Treatment (as a single agent) of chronic hepatitis C in patients with compensated liver disease in patients with contraindications or significant intolerance to other HCV antiviral drugs.
  • Note:
    • Current AASLD/IDSA guidelines do not recommend the use of interferon products. Peginterferon and ribavirin, typically combined with a direct-acting antiviral, remain in use for certain genotypes, particularly in resource-limited settings where newer interferon-free regimens are not available.
  • Limitations of use:
    • Peginterferon alfa-2a alone or combined with ribavirin without additional HCV antiviral drugs is not recommended for the treatment of patients with chronic HCV who didn't respond to ptior therapy with an interferon alfa.
    • Peginterferon alfa-2a is not recommended for treatment of patients with CHC with solid organ transplantation.

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Pegasys (Peginterferon Alfa-2a) Dose in Adults

Pegasys (Peginterferon Alfa-2a) Dose in the treatment of Chronic hepatitis C (monoinfection or coinfection with HIV):

• For treating chronic hepatitis C, the typical dose of Peginterferon Alfa-2a is 180 micrograms injected under the skin once a week.
• The length of treatment depends on factors like the type of hepatitis C virus and other antiviral medications being used.

Note:

• It's important to know that current guidelines from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) don't recommend using interferon products like Peginterferon Alfa-2a as the first choice for hepatitis C treatment.
• Instead, they suggest using newer medications called direct-acting antivirals.
• However, Peginterferon Alfa-2a might still be used in some situations, especially in places where the newer treatments are not available or affordable.

Pegasys (Peginterferon Alfa-2a) Dose in the treatment of Chronic hepatitis B:

• For treating chronic hepatitis B, the usual dose of Peginterferon Alfa-2a is 180 micrograms injected under the skin once a week.
• This treatment typically lasts for 48 weeks.

Missed dose:

• If you miss a dose and it's within 2 days of your usual injection day, you should take the missed dose as soon as you remember, and then continue with your regular schedule.
• But if it's more than 2 days after your usual injection day, you should contact your healthcare provider for guidance.

Pegasys (Peginterferon Alfa-2a) Dose in Children

Pegasys (Peginterferon Alfa-2a) Dose in the treatment of Chronic hepatitis B (CHB) infection (hepatitis B e antigen [HBeAg] positive):

• For children aged 3 years and older, as well as adolescents, with chronic hepatitis B (CHB) infection who test positive for hepatitis B e antigen (HBeAg), the typical dose of Peginterferon Alfa-2a is based on body surface area.
• The recommended dose is 104 micrograms per square meter of body surface area, administered by subcutaneous injection once a week. The maximum dose for each injection is 180 micrograms. The duration of therapy is usually 48 weeks.

Note:

• To calculate the dose, you multiply the body surface area (BSA) of the child or adolescent by 180 micrograms, then divide by 1.73 (the average body surface area for adults).
• Adolescents who turn 18 during treatment should continue with the pediatric dosing regimen.

Pegasys (Peginterferon Alfa-2a) Dose in the treatment of Chronic hepatitis C (CHC) infection:

• For children aged 5 years and older, as well as adolescents, with chronic hepatitis C (CHC) infection, the dose of Peginterferon Alfa-2a is determined based on body surface area (BSA).
• However, it's important to note that the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) do not recommend using interferon products for treating hepatitis C in children aged 3 to 11 years.
• The recommended dose is 104 micrograms per square meter of body surface area, administered by subcutaneous injection once weekly, with a maximum dose of 180 micrograms per dose.
• This is usually given in combination with ribavirin.

The duration of therapy varies depending on the genotype of the hepatitis C virus:

• For HCV genotypes 1, 4, 5, and 6, treatment typically lasts for 48 weeks.
• For HCV genotypes 2 and 3, treatment usually lasts for 24 weeks.

Pegasys (Peginterferon Alfa-2a) Dosing adjustment for toxicity:

Depression

• Mild Depression:
  • No dosage adjustment required.
  • Evaluate once weekly by visit/phone call.
  • If depression remains stable, continue weekly visits.
  • If depression improves, resume normal visit schedule.
  • If depression worsens after 8 weeks, consider psychiatric consultation; discontinue therapy or decrease dose to 78 mcg/m once weekly or a further dose reduction to 52 mcg/m once weekly.
• Moderate Depression:
  • Decrease dose to 78 mcg/m once weekly or a further dose reduction to 52 mcg/m once weekly.
  • Evaluate once weekly with an office visit at least every other week.
  • After 8 weeks, if symptoms improve and remain stable for 4 weeks, resume normal visit schedule; may continue reduced dosing or return to normal dose.
  • If depression remains stable, consider psychiatric evaluation and continue reduced dosing.
  • If symptoms worsen, obtain immediate psychiatric consultation and discontinue therapy permanently.
• Severe Depression:
  • Discontinue interferon treatment permanently.
  • Obtain immediate psychiatric consultation and therapy necessary.

Hematologic Toxicity

• Neutropenia:
  • ANC (Absolute Neutrophil Count) 750 to 999/mm :
    • CHB: No dosage modification.
    • CHC:
      • Week 1 to 2: Decrease dose to 78 mcg/m once weekly.
      • Weeks 3 to 48: No modification.
  • ANC 500 to 749/mm :
    • CHB: Decrease dose to 78 mcg/m once weekly.
    • CHC:
      • Week 1 to 2: Hold dose until ANC >750/mm then resume therapy at 78 mcg/m once weekly. Assess WBC (White Blood Cell count) 3 times weekly to verify ANC >750/mm .
      • Weeks 3 to 48: Decrease dose to 78 mcg/m once weekly.
  • ANC 250 to 499/mm :
    • CHB: Hold dose until ANC ≥1,000/mm , then resume dose at 52 mcg/m once weekly.
    • CHC:
      • Week 1 to 2: Hold dose until ANC >750/mm then resume dose at 52 mcg/m once weekly.
      • Weeks 3 to 48: Hold dose until ANC >750/mm then resume dose at 78 mcg/m once weekly.
  • ANC <250/mm or febrile neutropenia:
    • CHB, CHC: Discontinue treatment.
• Thrombocytopenia:
  • Platelet count 25,000 to <50,000/mm :
    • CHB, CHC: Decrease dose to 52 mcg/m once weekly.
  • Platelet count <25,000:
    • CHB, CHC: Discontinue treatment.

Pegasys (Peginterferon Alfa-2a) Pregnancy Category: C

• Peginterferon alfa-2a, a medication used to treat certain viral infections like hepatitis C, isn't recommended during pregnancy due to its potential negative effects on fetal growth and development, as noted in studies.
• While naturally occurring alfa interferon is found in normal amniotic fluid, studies show that the synthetic version of interferon alfa doesn't cross the placenta.
• Health guidelines advise against using peginterferon alfa-2a in pregnant women due to its effects, and animal studies have shown it can cause miscarriages.
• Treating hepatitis C during pregnancy isn't recommended either, as it doesn't decrease the risk of mother-to-child transmission and can pose risks to the developing fetus.
• Women with hepatitis C should consider delaying pregnancy until after completing treatment to reduce transmission risk.
• It's essential to confirm pregnancy status before administering peginterferon alfa-2a to women of reproductive age and to use reliable contraception due to potential menstrual cycle disruptions.
• Combination therapy with ribavirin, often used alongside peginterferon alfa-2a, is specifically contraindicated in pregnant women or their male partners due to the risk of birth defects and fetal death.
• All precautions regarding ribavirin use during pregnancy or concerning contraception should be strictly followed.

Use of peginterferon during breastfeeding

• Interferon alfa, a naturally occurring substance in breast milk, remains present even after administration of interferon alfa-2b medication, according to studies.
• Breastfeeding itself isn't known to spread hepatitis C virus, but it's advised to avoid breastfeeding if nipples are cracked or bleeding to prevent potential transmission.
• In cases of HIV co-infection, breastfeeding is not recommended.
• However, in other circumstances, breastfeeding is generally considered safe, provided there are no complications like cracked nipples, which could potentially expose the baby to the medication.

Pegasys (Peginterferon Alfa-2a) Dose in Kidney Disease:

• CrCl (Creatinine Clearance) ≥30 mL/minute: No dosage adjustment required.
• CrCl <30 mL/minute: 135 micrograms once weekly; monitor for toxicity.
• End-stage renal disease (ESRD) Requiring Hemodialysis: 135 micrograms once weekly; monitor for toxicity. If severe adverse reactions or laboratory abnormalities occur, dosage may be reduced to 90 micrograms once weekly until adverse reactions resolve. If intolerance persists after dosage adjustment, discontinuation may be necessary.

Pegasys (Peginterferon Alfa-2a) Dose in Liver disease:

Prior to Initiation:

• Contraindicated in autoimmune hepatitis, hepatic decompensation (Child-Pugh >6 [class B and C]) in cirrhotic patients before treatment, and hepatic decompensation with Child-Pugh ≥6 in cirrhotic HCV patients coinfected with HIV before treatment.

During Treatment:

• HCV:
  • If hepatic decompensation (Child-Pugh ≥6 [class B and C]) is observed, immediately discontinue therapy.
  • If ALT (Alanine Aminotransferase) progressively rises above baseline:
    • Decrease dose to 135 micrograms once weekly and monitor liver function tests (LFTs) more frequently.
    • If ALT continues to rise despite dose reduction or if ALT increase is accompanied by increased bilirubin or hepatic decompensation, discontinue therapy immediately. Therapy may resume after ALT flare subsides.
• HBV:
  • If ALT >5 times the upper limit of normal (ULN):
    • Consider decreasing dose to 135 micrograms once weekly or temporarily discontinuing and monitor LFTs more frequently.
    • If ALT continues to rise despite dose reduction or if ALT increase is accompanied by increased bilirubin or hepatic decompensation, discontinue therapy immediately. Therapy may resume after ALT flare subsides.
  • If ALT >10 times ULN:
    • Consider discontinuing therapy.

Common Side Effects of Pegasys (Peginterferon Alfa-2a):

• Central Nervous System:
  • Fatigue
  • Headache
  • Rigors
  • Insomnia
  • Anxiety
  • Irritability
  • Nervousness
  • Depression
  • Dizziness
  • Pain
• Dermatologic:
  • Alopecia
  • Pruritus
• Endocrine & Metabolic:
  • Growth Suppression
    • Weight
    • Height
• Gastrointestinal:
  • Nausea
  • Vomiting
  • Anorexia
  • Abdominal Pain
  • Diarrhea
• Hematologic & Oncologic:
  • Neutropenia
• Hepatic:
  • Increased Serum ALT
• Local:
  • Injection Site Reaction
• Neuromuscular & Skeletal:
  • Weakness
  • Myalgia
  • Arthralgia
• Respiratory:
  • Cough
  • Flu-Like Symptoms
• Miscellaneous:
  • Fever

Less Common Side Effects Of Pegasys (Peginterferon Alfa-2a):

• Central Nervous System:
  • Lack Of Concentration
  • Memory Impairment
  • Mood Changes
• Dermatologic:
  • Skin Rash
  • Dermatitis
  • Diaphoresis
  • Xeroderma
  • Eczema
• Endocrine & Metabolic:
  • Weight Loss
  • Hypothyroidism
  • Hyperthyroidism
• Gastrointestinal:
  • Decreased Appetite
  • Xerostomia
• Hematologic & Oncology:
  • Thrombocytopenia
  • Lymphocytopenia
  • Anemia
• Hepatic:
  • Increased Serum AST
  • Liver Decompensation
• Infection:
  • Bacterial Infection
• Neuromuscular & Skeletal:
  • Back Pain
• Ophthalmic:
  • Blurred Vision
• Respiratory:
  • Epistaxis
  • Upper Respiratory Tract Infection
  • Nasopharyngitis
  • Dyspnea

Contraindications to Pegasys (Peginterferon Alfa-2a):

• Hypersensitivity Reactions: Including urticaria, angioedema, bronchoconstriction, anaphylaxis, and Stevens-Johnson syndrome, to peginterferon alfa-2a, other alfa interferons, or any component of the formulation.
• Autoimmune Hepatitis: Contraindicated due to potential exacerbation of autoimmune conditions.
• Hepatic Decompensation: Contraindicated in cirrhotic patients with Child-Pugh score >6 (class B and C) before treatment, and in cirrhotic patients coinfected with chronic hepatitis C (CHC) and HIV with Child-Pugh score ≥6 before treatment.
• Neonates and Infants: Due to the presence of benzyl alcohol component in the formulation.
• Combination Therapy with Peginterferon Alfa-2a and Ribavirin: Contraindicated in pregnancy, men whose female partners are pregnant, patients with hemoglobinopathies (such as thalassemia major, sickle cell disease), and in combination with didanosine.
• Limited Documentation of Allergenic Cross-Reactivity: While documentation of allergenic cross-reactivity for interferons is limited, due to similarities in chemical structure and pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
• Additional Contraindications in Canadian Labeling (not in US labeling): Hypersensitivity to E. coli-derived products; history of autoimmune disease; severe psychiatric disorder or history of severe psychiatric disorder; uncontrolled thyroid disorder; breastfeeding.

Warnings and precautions

Suppression of bone marrow

• May cause severe cytopenias and rarely aplastic anemia.
• Ribavirin may enhance these effects.
• Caution required with baseline neutrophil count <1,500/mm³, platelet count <90,000/mm³, or hemoglobin <10 g/dL.
• Discontinue therapy if ANC <500/mm³ or platelet count <25,000/mm³.

CNS depression:

• May impair physical or mental abilities. Patients cautioned against tasks requiring mental alertness like operating machinery or driving.

Dermatologic effects

• Serious skin reactions including Stevens-Johnson syndrome reported. Discontinue with signs of severe skin reactions.

Gastrointestinal effects:

• May cause gastrointestinal hemorrhage, ulcerative colitis, and hemorrhagic/ischemic colitis. Discontinue immediately if symptoms of colitis develop.

Hepatic effects

• Hepatic decompensation and death observed, especially in cirrhotic patients.
• Monitor hepatic function closely; discontinue immediately if decompensation occurs.

Hypersensitivity reactions

• Severe acute hypersensitivity reactions reported. Prompt discontinuation recommended.

Neuropsychiatric disorders [US Boxed Warning]

• May cause or worsen life-threatening neuropsychiatric disorders. Monitor closely; discontinue treatment with worsening symptoms.

Ophthalmic effects

• Vision problems including decreased or loss of vision and retinopathy reported. Prompt eye exam recommended if ocular symptoms occur.

Pancreatitis

• Withhold treatment for suspected pancreatitis; discontinue for confirmed cases.

Effects on the pulmonary system:

• May cause or worsen respiratory conditions like dyspnea and pneumonia. Discontinue with pulmonary infiltrates or impaired function.

Autoimmune disease: [US-Boxed Warning]

• May cause or exacerbate autoimmune disorders. Monitor closely; discontinue in severe cases.

Cardiovascular disease

• Caution in patients with prior cardiovascular disease; observe for hypertension, arrhythmias, chest pain, and myocardial infarction.

Diabetes:

• Caution in patients with diabetes mellitus; monitor glucose levels closely.

Hepatitis B:

• Flares in serum ALT may occur; monitor LFTs closely and consider dose reduction.

Infectious disorders: [US Boxed Warning]:

• May cause or worsen infectious disorders; monitor closely and discontinue in severe cases.

Ischemic disorders: [US Boxed Warning]:

• May cause or worsen ischemic disorders and cerebrovascular events; monitor closely and discontinue in severe cases.

Renal impairment

• Use with caution in renal dysfunction; dosage adjustment and monitoring required.

Seizure disorders:

• Not recommended in patients with uncontrolled seizures.

Thyroid disorders:

• Use with caution in patients with thyroid disease; monitor and discontinue if unable to manage effectively.

Peginterferon (peginterferon) alfa-2a: Drug Interaction

Risk Factor C (Monitor therapy)
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
CloZAPine	CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Methadone	Interferons (Alfa) may increase the serum concentration of Methadone.
Pegloticase	May diminish the therapeutic effect of PEGylated Drug Products.
Pegvaliase	PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ribavirin (Oral Inhalation)	Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Hemolytic anemia has been observed.
Ribavirin (Systemic)	Interferons (Alfa) may enhance the adverse/toxic effect of Ribavirin (Systemic). Hemolytic anemia has been observed.
Theophylline Derivatives	Interferons may decrease the metabolism of Theophylline Derivatives. Exceptions: Dyphylline.
Zidovudine	Interferons may enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine.
Risk Factor D (Consider therapy modification)
Aldesleukin	Interferons (Alfa) may enhance the adverse/toxic effect of Aldesleukin. In particular, risks of myocardial and renal toxicity may be increased by this combination.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
TiZANidine	CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Telbivudine	Peginterferon Alfa-2a may enhance the adverse/toxic effect of Telbivudine. Specifically, the risk for peripheral neuropathy may be increased.

Monitoring parameters:

Manufacturer's Labeling: Clinical Study Assessments

Pediatric Patients:

• Hematologic and biochemical assessments:
  • Weeks 1, 3, 5, and 8
  • Every 4 weeks thereafter
• TSH measured every 12 weeks

Adults:

• CBC (including hemoglobin, WBC, and platelets) and chemistries (including liver function tests and uric acid):
  • Weeks 1, 2, 4, 6, and 8
  • Every 4-6 weeks thereafter (more frequently if abnormal)
• TSH measured every 12 weeks

Baseline Entrance Criteria for Adults:

• Platelet count ≥90,000/mm³ (as low as 75,000/mm³ in patients with cirrhosis or 70,000/mm³ in patients with CHC coinfected with HIV)
• ANC ≥1,500/mm³
• Serum creatinine <1.5 times ULN
• TSH and T within normal limits or adequately controlled
• CD4 cell count ≥200 cells/mm³ or CD4 cell count ≥100 cells/mm³ but <200 cells/mm³ and HIV-1 RNA <5,000 copies/mL in CHC patients coinfected with HIV
• Hemoglobin ≥12 g/dL for women and ≥13 g/dL for men in CHC monoinfected patients
• Hemoglobin ≥11 g/dL for women and ≥12 g/dL for men in CHC patients coinfected with HIV
• Serum HCV RNA levels (pretreatment, 12- and 24 weeks after therapy initiation, 24 weeks after completion of therapy)

Additional Recommendations:

• Prior to treatment: Pregnancy screening for women of childbearing age receiving treatment or having male partners receiving treatment. Monthly pregnancy tests up to 6 months after ribavirin combination therapy discontinuation.
• Evaluate for depression and psychiatric symptoms before and during therapy.
• Baseline eye examination and periodic evaluations for patients with baseline eye disorders.
• Baseline echocardiogram for patients with cardiac disease.
• In children: Monitor growth velocity and weight during and after combination therapy discontinuation.

Alternate Recommendations for Chronic Hepatitis B (AASLD [Terrault 2016]):

• During therapy: CBC (monthly to every 3 months); TSH (every 3 months); monitor for autoimmune, ischemic, neuropsychiatric, and infectious complications.

How to administer Pegasys (Peginterferon Alfa-2a)?

Subcutaneous Administration Guidelines:

• Injection Site: Administer in the abdomen or thigh.
• Rotation: Rotate injection site for each dose to prevent irritation or discomfort.
• Consistency: Administer on the same day and at approximately the same time each week for consistency in treatment schedule.

Mechanism of action of Pegasys (Peginterferon Alfa-2a):

• Alpha interferons, a group of proteins produced by nucleated cells, have antiviral and antiproliferative properties as well as immune-regulating activities.
• There are 16 types of alpha interferons.
• Interferons are able to interact with cells through high-affinity cell surface receptors.
• Multiple effects can be observed after activation including induction gene transcription.
• Interferons can inhibit cell growth, alter the state cellular differentiation, interfere oncogene gene expression, alter cell membrane antigen expression, enhance phagocytic activity, augment cytotoxicity and lymphocytes for target tissues.

Half-life elimination:

• Terminal: The time it takes for half of the medication to be eliminated from the body ranges from 50 to 160 hours. This duration may be longer in individuals with renal dysfunction.

Time to peak, serum:

• The medication reaches its peak concentration in the bloodstream between 72 to 96 hours after administration.

International Brand Names of Peginterferon Alfa-2a:

• Pegasys
• Pegasys ProClick
• Optipeg-A
• Pegasys
• Pegasys PFS
• Pegferon
• Pegin

Peginterferon Alfa-2a Brand Names in Pakistan:

Peginterferon Alfa-2a Injection 180 Mcg In Pakistan
Peg	Ferozsons Laboratoies Ltd.

 

Peginterferon Alfa-2a Injection 180 Mcg/Ml In Pakistan
Unipeg	Getz Pharma Pakistan (Pvt) Ltd.

 

Peginterferon Alfa-2a Injection 180 Mcg/0.5ml In Pakistan
Peg-Inf	Ferozsons Laboratoies Ltd.
Pegasys	Roche Pakistan Ltd.
Ropegra	Roche Pakistan Ltd.
Taget	Hilton Pharma (Pvt) Limited