Schedule H

Subcutaneous (SC), Intravenous (IV — inpatient/specialist use only)

• Injection: 100 IU/mL in 10 mL vials

• Injection: 100 IU/mL in 3 mL cartridges (for pen devices)

• Injection: 100 IU/mL in 3 mL pre-filled pens (KwikPen)

• Concentrated formulation: 200 IU/mL in 3 mL pre-filled pens

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 1 Diabetes Mellitus — Prandial Insulin Component

Parameter Recommendation

Starting dose 0.1–0.2 units/kg per meal SC (typically 40–50% of total daily insulin as prandial component)

Titration Adjust by 1–2 units every 2–3 days based on 2-hour postprandial glucose (target: <180 mg/dL)

Usual maintenance dose 0.15–0.25 units/kg per meal; total prandial insulin typically 40–50% of TDD

Maximum dose Individualised; no fixed ceiling; guided by glycaemic targets

Clinical Notes:

• Administer 0–15 minutes before meals or immediately after starting meal

• Must be used with basal insulin (glargine, detemir, degludec, or NPH) as part of basal-bolus regimen

• Suitable for continuous subcutaneous insulin infusion (CSII/pump therapy)

• Onset: 15–30 minutes; Peak: 0.5–2.5 hours; Duration: 3–5 hours

• Insulin-to-carbohydrate ratio allows precise dose calculation per meal

1. Type 2 Diabetes Mellitus — Prandial Insulin in Intensification Regimens

Parameter Recommendation

Starting dose 4–6 units SC before the largest meal OR 10% of basal insulin dose per meal

Titration Increase by 1–2 units twice weekly based on postprandial glucose

Usual maintenance dose 4–12 units per meal; adjust based on meal size and composition

Maximum dose Individualised; often 0.5–1.0 units/kg/day as total prandial component

Clinical Notes:

• Indicated when basal insulin alone fails to achieve glycaemic targets

• Can be initiated as basal-plus (one prandial dose) and escalated to basal-bolus (three prandial doses)

• Reduce sulfonylurea dose when adding prandial insulin to minimise hypoglycaemia

• May be used in premixed formulations (Humalog Mix 25/75, Mix 50/50)

1. Diabetic Ketoacidosis (DKA) — Intravenous Use

Parameter Recommendation

Starting dose 0.1 units/kg IV bolus (optional; may omit if glucose <250 mg/dL) followed by 0.1 units/kg/hour continuous IV infusion

Titration Adjust infusion rate to achieve glucose reduction of 50–75 mg/dL/hour

Usual maintenance dose 0.05–0.1 units/kg/hour; reduce to 0.02–0.05 units/kg/hour when glucose <200 mg/dL

Maximum dose Guided by glucose response

Clinical Notes:

• Regular insulin remains preferred for IV use; lispro may be used when regular insulin unavailable

• Initiate only after fluid resuscitation commenced

• Continue IV insulin until anion gap closes and patient can tolerate oral intake

• Transition to SC insulin with 1–2 hour overlap before discontinuing IV infusion

• Monitor hourly: blood glucose, electrolytes (especially potassium)

1. Continuous Subcutaneous Insulin Infusion (CSII/Insulin Pump Therapy)

Parameter Recommendation

Starting dose Total daily dose (TDD) reduced by 20–25% from prior MDI regimen; 50% as basal rate, 50% as boluses

Titration Adjust basal rates and bolus ratios based on CGM/SMBG patterns

Usual maintenance dose Highly individualised; basal rates typically 0.3–0.6 units/hour

Maximum dose No fixed ceiling

Clinical Notes:

• Insulin lispro is suitable for pump use due to stable pharmacokinetics

• Specialist initiation and ongoing supervision mandatory

Secondary Indications — Adults (Off-label, if any)

Indication Dose Duration Label Status Evidence Basis

Hyperglycaemia management in ICU/critical care 0.5–2 units/hour IV infusion; titrate hourly to target glucose 140–180 mg/dL Duration of critical illness OFF-LABEL; Specialist only AIIMS ICU protocols

Hyperglycaemia with total parenteral nutrition Tailored to glucose concentration and infusion rate; typically add to TPN bag Duration of TPN OFF-LABEL; Specialist only Indian hospital protocols for critical care

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 1 Diabetes Mellitus in Children ≥3 Years

3–5 years 0.5–1 unit per meal Increase by 0.5 units every 3–5 days based on postprandial glucose 0.1–0.15 units/kg per meal Conservative dosing; high hypoglycaemia risk

6–12 years 1–4 units per meal Increase by 1 unit every 2–3 days 0.15–0.25 units/kg per meal Part of basal-bolus regimen

13–18 years 4–8 units per meal Increase by 1–2 units every 2–3 days 0.2–0.3 units/kg per meal Higher requirements during puberty

Clinical Notes:

• Total daily insulin requirement in children: 0.5–1.0 units/kg/day (higher during puberty: up to 1.5 units/kg/day)

• Prandial insulin typically constitutes 40–50% of total daily dose

• Administer immediately before meals; may give immediately after meal in young children with unpredictable eating

• Target postprandial glucose: <180 mg/dL (individualise based on age)

Safety Monitoring:

• SMBG minimum 4–6 times daily (premeal, 2-hour postprandial, bedtime)

• Monitor for hypoglycaemia, especially nocturnal and during physical activity

• Assess injection sites for lipohypertrophy at each visit

• HbA1c every 3 months

• Growth and weight monitoring

• Parental/caregiver education on hypoglycaemia recognition and treatment mandatory

Secondary Indications — Paediatrics (Off-label, if any)

Indication Dose Duration Label Status Evidence Basis

Hyperglycaemia with enteral/parenteral nutrition Individualised; typically 0.05–0.1 units/kg/hour IV infusion Duration of nutritional support OFF-LABEL; Specialist only Indian PICU practice

CSII/Pump therapy in children Individualised; TDD reduced by 20–25% from MDI; 50% basal, 50% boluses Long-term Approved ≥3 years; Specialist only IAP Paediatric Endocrinology guidelines

Age Restriction: Not recommended in children below 3 years of age except under specialist paediatric endocrinology supervision with appropriate monitoring capability.

Clinical Notes:

• Renal impairment reduces insulin clearance and gluconeogenesis

• Insulin requirements typically decrease as CKD progresses

• More frequent glucose monitoring essential in CKD stages 4–5

• Hypoglycaemia (active episode)

• Known hypersensitivity to insulin lispro or any excipient in the formulation

• Renal impairment (increased hypoglycaemia risk)

• Hepatic impairment (impaired gluconeogenesis)

• Hypoglycaemia unawareness

• Gastroparesis (unpredictable meal absorption may cause mismatch with insulin action)

• Adrenal or pituitary insufficiency (increased hypoglycaemia risk)

• Erratic meal patterns or variable carbohydrate intake

• Intercurrent illness, infection, or stress (may alter insulin requirements)

• Hypokalaemia or risk of hypokalaemia (especially with IV use)

• Lipohypertrophy from repeated injection at same site (causes erratic absorption)

• Visual or cognitive impairment (risk of dosing errors)

• Switching between insulin formulations or concentrations (dose may need adjustment)

Parameter Recommendation

Safety status Safe in pregnancy; extensive human data support use

Preferred status Rapid-acting insulin analogues (lispro, aspart) are acceptable alternatives to regular insulin in Indian obstetric practice

When to use Gestational diabetes mellitus (GDM) requiring insulin; pre-existing Type 1 or Type 2 diabetes during pregnancy

Monitoring Frequent SMBG (6–8 times daily); HbA1c monthly; fetal growth monitoring; adjust dose each trimester

Clinical Notes:

• Insulin requirements typically increase during 2nd and 3rd trimesters

• Risk of hypoglycaemia increased in 1st trimester

• Insulin requirements drop rapidly post-delivery

• Better postprandial control with lispro compared to regular insulin may benefit pregnancy outcomes

• Endocrinology and obstetric co-management recommended

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Negligible; insulin is a large peptide molecule degraded in infant GI tract

Preferred alternative Any insulin (human or analogue) acceptable during lactation

Infant monitoring No specific monitoring required; observe normal feeding and growth

Clinical Notes:

• Breastfeeding increases maternal glucose utilisation; insulin dose may need reduction

• Ensure adequate maternal caloric intake to prevent hypoglycaemia

• Starting dose: Conservative; start at lower end of dosing range (e.g., 2–4 units per meal or 0.1 units/kg per meal)

• Titration: Slower; increase every 5–7 days rather than 2–3 days

• Extra risks:

• Hypoglycaemia more common and more dangerous (risk of falls, cardiac events, cognitive decline)

• Hypoglycaemia unawareness may be present

• Reduced renal function (even with normal serum creatinine)

• Polypharmacy increasing interaction risk

• Visual and cognitive impairment affecting self-administration

• Erratic meal patterns

• Recommendations:

• Less stringent glycaemic targets may be appropriate (HbA1c 7.5–8.5%)

• Simplified regimens preferred

• Consider caregiver involvement in insulin administration

• Assess injection technique and meal timing at each visit

Interacting Drug/Class Mechanism/Effect Recommendation

Beta-blockers (especially non-selective) Mask hypoglycaemia symptoms (tremor, tachycardia); may prolong hypoglycaemia Use cardioselective beta-blockers if needed; educate on neuroglycopenic symptoms

Sulfonylureas and meglitinides Additive hypoglycaemic effect Monitor closely; may need dose reduction of either agent

MAO inhibitors Enhanced hypoglycaemic effect Monitor glucose closely; reduce insulin dose if needed

Pentamidine May cause profound hypoglycaemia followed by hyperglycaemia Avoid if possible; close glucose monitoring if essential

Systemic corticosteroids Significant increase in insulin resistance May require substantial insulin dose increase; adjust on steroid initiation/cessation

Alcohol (excessive) Potentiates hypoglycaemia; impairs counter-regulatory response Counsel on risks; avoid excess; ensure food intake with alcohol

Interacting Drug/Class Mechanism/Effect Recommendation

ACE inhibitors / ARBs May enhance insulin sensitivity Monitor for hypoglycaemia when initiating

Thiazide diuretics May cause hyperglycaemia May require insulin dose increase

Fluoroquinolones Unpredictable glycaemic effects (hypo- or hyperglycaemia) Monitor blood glucose closely

Thiazolidinediones (pioglitazone) Additive hypoglycaemic effect; fluid retention risk Monitor for oedema and hypoglycaemia

SGLT-2 inhibitors Additive glucose-lowering; risk of euglycaemic DKA Reduce insulin dose; educate on ketoacidosis symptoms

Rifampicin May alter metabolism of concomitant OADs Monitor and adjust therapy accordingly

Salicylates (high-dose) May enhance hypoglycaemic effect Monitor glucose if high-dose salicylates used

• Hypoglycaemia (most common and dose-limiting)

• Injection site reactions (pain, erythema, pruritus)

• Lipohypertrophy at injection sites

• Weight gain

• Peripheral oedema (usually mild and transient)

• Severe hypoglycaemia (neuroglycopenia, seizures, loss of consciousness, coma) — requires immediate intervention with glucose/glucagon

• Hypokalaemia (especially with IV insulin; can precipitate arrhythmias)

• Anaphylaxis and severe systemic allergic reactions (rare) — requires immediate discontinuation

• Severe local allergic reactions

• Lipoatrophy at injection sites (rare with analogues)

After initiation/dose change SMBG premeal and 2-hour postprandial (minimum 4 times daily); watch for hypoglycaemia; review injection technique

Long-term HbA1c every 3 months; weight at each visit; injection site inspection at each visit (for lipohypertrophy); annual renal function, lipid profile, retinal examination, foot examination

Insulin Lispro 100 IU/mL:

• Humalog® (Eli Lilly) — KwikPen, cartridge, vial

• Lupinsulin Lispro® (Lupin)

• Lisprorapid® (Wockhardt)

Insulin Lispro 200 IU/mL (concentrated):

• Humalog® 200 (Eli Lilly) — KwikPen

Premixed Formulations (Lispro + Lispro Protamine):

• Humalog Mix 25® (25% lispro, 75% lispro protamine)

• Humalog Mix 50® (50% lispro, 50% lispro protamine)

Fixed-Dose Combinations:

Note: Verify formulation and concentration before dispensing; 100 IU/mL and 200 IU/mL are NOT interchangeable without dose adjustment.

NLEM Status: Rapid-acting insulin analogues (lispro) are NOT included in NLEM 2022; not NPPA price-controlled.

Government Supply: Limited availability through government hospitals; primarily available in private sector.

• Insulin lispro has faster onset (15–30 minutes) and shorter duration (3–5 hours) compared to regular insulin (30–60 minutes onset, 5–8 hours duration) — allows dosing immediately before or with meals without the 30-minute wait required for regular insulin

• For young children with unpredictable eating, insulin lispro can be given immediately after the meal based on actual carbohydrate consumed — this flexibility is a significant advantage over regular insulin

• Switching from regular insulin to lispro typically reduces postprandial glucose spikes and may decrease late postprandial hypoglycaemia risk

• Systematic rotation of injection sites is critical to prevent lipohypertrophy, which causes erratic absorption and glycaemic variability

• When using concentrated (200 IU/mL) formulation, ensure prescribing clarity to avoid dosing errors — the pen delivers same units but in half the volume

• In CSII/pump therapy, insulin lispro is preferred over regular insulin due to more predictable pharmacokinetics and reduced occlusion risk

insulin; rapid-acting; diabetes; Type 1 DM; Type 2 DM; prandial insulin; CSII; insulin pump; pregnancy-safe; paediatric-use; hypoglycaemia-risk

RxIndia v1.0 — 29 May 2025

• CDSCO product database

• Indian Pharmacopoeia / National Formulary of India

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 1 and Type 2 Diabetes

• AIIMS Endocrinology Protocols

• IAP Guidelines for Paediatric and Adolescent Diabetes

• Eli Lilly prescribing information (supportive)

• WHO Model Formulary (supportive)