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

• Faster-acting formulation (Fiasp®): 100 IU/mL in 3 mL cartridges and 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 30–50% of total daily insulin as prandial)

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 immediately before meals (0–15 minutes) or within 20 minutes 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: 10–20 minutes; Peak: 1–3 hours; Duration: 3–5 hours

• Carbohydrate counting allows precise dose calculation per meal

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

Parameter Recommendation

Starting dose 4 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 (biphasic insulin aspart 30:70)

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; if no response, may double infusion rate

Clinical Notes:

• IV insulin aspart may be used when regular insulin is unavailable; regular insulin remains preferred

• 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 aspart is suitable for pump use due to stable pharmacokinetics

• Specialist initiation and ongoing supervision mandatory

• Faster-acting formulation (Fiasp®) may provide improved postprandial control in pumps

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; NICE-SUGAR study principles

Perioperative glycaemic control Variable rate IV insulin infusion per institutional protocol Perioperative period OFF-LABEL; Specialist only Indian hospital protocols

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 1 Diabetes Mellitus in Children ≥1 Year

1–5 years 0.5–1 unit per meal Increase by 0.5 units every 3–5 days based on postprandial glucose 0.1–0.2 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 unpredictable eaters (young children)

• Target postprandial glucose: <180 mg/dL (age-appropriate targets)

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

Diabetic Ketoacidosis in Children — Intravenous Use

Parameter Recommendation

Starting dose 0.05–0.1 units/kg/hour IV infusion (NO IV bolus in children)

Titration Maintain glucose reduction of 50–75 mg/dL/hour; reduce rate if faster decline

Usual maintenance dose 0.05 units/kg/hour; reduce further when glucose <250–300 mg/dL

Maximum dose 0.1 units/kg/hour initially

Clinical Notes:

• IV bolus NOT recommended in paediatric DKA due to risk of cerebral oedema

• Begin insulin infusion 1–2 hours after fluid resuscitation commenced

• Add 5% dextrose to IV fluids when glucose <250–300 mg/dL

• Monitor neurological status closely; signs of cerebral oedema include headache, altered sensorium, bradycardia

• Use insulin aspart IV only if regular insulin unavailable

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

Indication Dose Duration Label Status Evidence Basis

CSII/Pump therapy in children Individualised; TDD reduced by 20–25% from MDI; 50% basal, 50% boluses Long-term OFF-LABEL below 2 years; Specialist only IAP Paediatric Endocrinology guidelines; international pump protocols

Age Restriction: Not recommended in children below 1 year 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 aspart 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)

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

• Visual or cognitive impairment (risk of dosing errors)

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

Parameter Recommendation

Safety status Safe in pregnancy; extensive human data support use

Preferred status Rapid-acting insulin analogues (aspart, lispro) 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

• Closer postprandial control with insulin aspart 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)

• 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 (basal-plus rather than full basal-bolus if possible)

• 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 Monitor blood glucose closely

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

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

Thyroid hormones May increase insulin requirements May require dose adjustment during thyroid replacement

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

Octreotide Variable effect on insulin requirements Monitor closely; may increase or decrease requirements

• Hypoglycaemia (most common and dose-limiting)

• Injection site reactions (pain, erythema, pruritus)

• Lipohypertrophy at injection sites

• Weight gain

• Peripheral oedema (usually mild and transient)

• Nasopharyngitis (reported in clinical trials)

• 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)

• Severe local allergic reactions

• Lipoatrophy at injection sites (rare with analogues)

• Insulin antibody formation (rare; may affect glycaemic control)

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

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

IV insulin use Hourly blood glucose; electrolytes (especially potassium) every 2–4 hours

Insulin Aspart:

• NovoRapid® (Novo Nordisk) — FlexPen, Penfill cartridge, vial

• NovoRapid® PumpCart (for insulin pumps)

Faster-Acting Insulin Aspart:

• Fiasp® (Novo Nordisk) — FlexTouch pen, Penfill cartridge

Biphasic Insulin Aspart (premixed 30:70):

• NovoMix® 30 (Novo Nordisk)

Note: Limited biosimilar availability in India; verify formulation and device compatibility.

NLEM Status: Insulin injection (soluble) is included in NLEM 2022; rapid-acting analogues (aspart) are not specifically listed but price regulation applies to certain formulations.

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

• Insulin aspart has faster onset (10–20 minutes) and shorter duration (3–5 hours) compared to regular insulin (30–60 minutes onset, 5–8 hours duration) — allows dosing immediately before meals without the 30-minute wait required for regular insulin

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

• Faster-acting insulin aspart (Fiasp®) contains additional excipients allowing even faster absorption; may provide better postprandial control but is not essential for most patients

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

• Do NOT mix insulin aspart with other insulins in the same syringe except as per manufacturer-specified premixed formulations

• In CSII/pump therapy, insulin aspart 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 diabetes; hypoglycaemia-risk

RxIndia v1.0 — 29 May 2025

• CDSCO product database

• Indian Pharmacopoeia / National Formulary of India

• NLEM 2022

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes

• AIIMS Endocrinology and ICU Protocols

• IAP Guidelines for Paediatric and Adolescent Diabetes

• ISPAD Clinical Practice Consensus Guidelines (supportive reference for paediatric diabetes)

• Novo Nordisk prescribing information (supportive)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive pharmacologic detail)