Schedule H

Subcutaneous (SC)

• Injection: 40 IU/mL in 10 mL vials

• 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

Composition: 70% Isophane insulin (NPH/intermediate-acting) + 30% Soluble insulin (Regular/short-acting)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 2 Diabetes Mellitus — When Oral Agents Are Inadequate

Parameter Recommendation

Starting dose 0.2–0.3 units/kg/day SC in 2 divided doses OR 10–12 units before breakfast and 6–8 units before dinner

Titration Increase by 2–4 units every 3–4 days based on fasting and pre-dinner glucose (target: fasting 80–130 mg/dL)

Usual maintenance dose 0.4–0.8 units/kg/day in 2 divided doses

Maximum dose Individualised; no fixed ceiling; guided by glycaemic targets and hypoglycaemia risk

Typical Dose Distribution:

• Morning dose (before breakfast): ~⅔ of total daily dose

• Evening dose (before dinner): ~⅓ of total daily dose

• Alternative: 50:50 split if patient has substantial dinner and light breakfast

Clinical Notes:

• Administer 30–45 minutes before meals to allow for regular insulin onset

• Requires consistent meal timing and carbohydrate content

• Less flexible than basal-bolus regimens; suitable for patients with regular lifestyle

• May be combined with metformin and/or other oral agents

1. Type 1 Diabetes Mellitus — When Basal-Bolus Regimen Not Feasible

Parameter Recommendation

Starting dose 0.4–0.6 units/kg/day SC in 2 divided doses

Titration Increase by 2–4 units every 3–4 days based on SMBG patterns

Usual maintenance dose 0.6–1.0 units/kg/day in 2 divided doses

Maximum dose Individualised; typically 1.0–1.5 units/kg/day; guided by glycaemic targets

Clinical Notes:

• Basal-bolus regimen with separate basal and prandial insulins is preferred for optimal control

• Pre-mixed insulin may be used when patient preference, cost, or adherence issues favour simplified regimen

• Less flexibility for dose adjustments; may result in suboptimal glycaemic control

• May require supplemental regular insulin for mid-day meal coverage

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

Indication Dose Duration Label Status Evidence Basis

Gestational Diabetes Mellitus (GDM) Starting: 0.3–0.5 units/kg/day in 2 divided doses; titrate based on glucose targets Duration of pregnancy OFF-LABEL; Specialist only Indian tertiary centre practice (AIIMS); used when basal-bolus not practical

Steroid-induced hyperglycaemia Starting: 0.2–0.3 units/kg/day; adjust based on glucose monitoring Duration of steroid therapy OFF-LABEL; Specialist only Indian hospital protocols

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 1 Diabetes Mellitus in Children ≥4 Years

4–6 years 0.3–0.4 units/kg/day in 2 divided doses Increase by 1–2 units every 3–5 days based on SMBG 0.5–0.7 units/kg/day High hypoglycaemia risk; conservative dosing

7–12 years 0.4–0.5 units/kg/day in 2 divided doses Increase by 2 units every 3–4 days 0.6–0.9 units/kg/day

13–18 years 0.5–0.7 units/kg/day in 2 divided doses Increase by 2–4 units every 3–4 days 0.8–1.2 units/kg/day Higher requirements during puberty

Dose Distribution:

• Morning (before breakfast): ~⅔ of total daily dose

• Evening (before dinner): ~⅓ of total daily dose

Clinical Notes:

• Basal-bolus regimen preferred in Type 1 DM for optimal glycaemic control; pre-mixed insulin is a compromise option

• Administer 30 minutes before meals

• Requires consistent meal timing — difficult in children with variable appetite

Safety Monitoring:

• SMBG at least 3–4 times daily (fasting, pre-dinner, bedtime; postprandial if needed)

• Monitor for nocturnal hypoglycaemia (bedtime glucose, mid-sleep glucose if symptomatic)

• HbA1c every 3 months

• Growth and weight monitoring at each visit

• Injection site inspection for lipohypertrophy

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

Indication Dose Duration Label Status Evidence Basis

Type 2 Diabetes Mellitus in adolescents Starting: 0.3–0.5 units/kg/day in 2 divided doses; titrate as per T2DM protocol Long-term OFF-LABEL; Specialist only IAP guidelines; limited paediatric data

Age Restriction: Not recommended in children below 4 years of age except under specialist paediatric endocrinology supervision.

Clinical Notes:

• Insulin clearance is reduced in renal impairment, prolonging insulin action

• Pre-mixed formulations offer less flexibility for dose adjustment compared to basal-bolus regimens

• Consider switching to separate basal and prandial insulins in significant renal impairment

• Hypoglycaemia (active episode)

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

• Diabetic ketoacidosis (requires IV regular insulin for initial management)

• Intravenous administration (not approved for IV use)

• Renal impairment (reduced insulin clearance; increased hypoglycaemia risk)

• Hepatic impairment (impaired gluconeogenesis)

• Elderly patients (hypoglycaemia unawareness; erratic meals)

• Irregular meal patterns or shift work (pre-mixed insulin requires consistent timing)

• Hypoglycaemia unawareness

• Gastroparesis (unpredictable meal absorption)

• Adrenal or pituitary insufficiency

• Intercurrent illness or stress (may alter insulin requirements)

• Concurrent use of beta-blockers (may mask hypoglycaemia symptoms)

• Lipohypertrophy from repeated injection at same site

• Cognitive or visual impairment (dosing errors)

• Patients requiring fine glycaemic control (basal-bolus regimen preferred)

Parameter Recommendation

Safety status Human insulin is safe in pregnancy; does not cross placenta

Preferred alternative Basal-bolus regimen (NPH + Regular insulin) preferred for tighter glycaemic control in GDM and pre-existing diabetes

When to use May be used when patient adherence, cost, or lifestyle factors favour simplified regimen; specialist supervision recommended

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

• Pre-mixed insulin offers less flexibility for postprandial glucose control compared to basal-bolus

• Endocrinology and obstetric co-management recommended

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Not applicable; insulin is a large peptide molecule degraded in infant GI tract

Preferred alternative Any insulin regimen 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; 0.1–0.2 units/kg/day or 6–10 units twice daily

• Titration: Slower; increase every 5–7 days rather than 3–4 days

• Extra risks:

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

• Hypoglycaemia unawareness frequently present

• Reduced renal function (even with normal serum creatinine)

• Irregular meal patterns common

• Polypharmacy increasing interaction risk

• Visual and cognitive impairment affecting self-administration

• Recommendations:

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

• Pre-mixed insulin may be suitable due to simplified regimen (fewer injections)

• Ensure consistent meal timing and carbohydrate intake

• Consider caregiver involvement in insulin administration

• Regular assessment of injection technique

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 oral agent

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

Systemic corticosteroids Significant increase in insulin resistance May require substantial insulin dose increase (sometimes 2–3 fold); 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 and oedema risk Monitor for oedema and heart failure; may need insulin dose reduction

Sulfonamides (co-trimoxazole) May enhance hypoglycaemic effect Monitor glucose closely

Rifampicin May alter glucose metabolism Monitor and adjust therapy accordingly

Isoniazid May cause hyperglycaemia Monitor glucose; may need insulin dose adjustment

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

• Hypoglycaemia (most common and dose-limiting; especially with irregular meals)

• 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; may require hospitalisation

• Hypokalaemia (with high doses or during correction of hyperglycaemia)

• Anaphylaxis and severe systemic allergic reactions (rare)

• Generalised urticaria

• Lipoatrophy at injection sites (rare with human insulin)

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

After initiation/dose change SMBG at least 3 times daily (fasting, pre-dinner, bedtime); additional postprandial glucose if needed; monitor for hypoglycaemia

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

Human Premixed Insulin 70/30 (40 IU/mL and 100 IU/mL):

• Mixtard® 30 (Novo Nordisk) — Penfill, FlexPen, vial

• Human Mixtard® 30/70 (Novo Nordisk)

• Huminsulin® 30/70 (Eli Lilly)

• Insuman® Comb 30 (Sanofi)

• Wosulin® 30/70 (Wockhardt)

• Insugen® 30/70 (Biocon)

• Recosulin® 30/70 (Ranbaxy/Sun Pharma)

• Human Insulin 30/70 IP (multiple generic manufacturers)

Other Premix Ratios Available:

• 25/75 formulations (less common)

Note: Verify formulation ratio and concentration (40 IU/mL vs 100 IU/mL) before dispensing; use matching syringes.

NLEM Status: Biphasic Isophane Insulin (Human) 70/30 is included in NLEM 2022; NPPA price-controlled.

Government Supply: Widely available through government hospitals, NHM, and Jan Aushadhi stores at subsidised rates.

• Pre-mixed 70/30 insulin requires consistent meal timing and carbohydrate intake — emphasise this during patient counselling; not suitable for patients with irregular schedules or shift work

• Administer 30–45 minutes before meals to allow regular insulin component to act; failure to do so results in postprandial hyperglycaemia followed by late hypoglycaemia

• The fixed 70:30 ratio limits flexibility; if patient has persistent fasting hyperglycaemia despite adequate pre-dinner dose, or frequent nocturnal hypoglycaemia, consider switching to basal-bolus regimen

• Gently roll the vial/cartridge to resuspend the cloudy isophane component before each injection; do not shake vigorously

• Systematic rotation of injection sites is essential to prevent lipohypertrophy, which causes erratic insulin absorption

• In elderly patients with simplified needs and regular meal patterns, pre-mixed insulin offers advantages of fewer injections while providing both basal and prandial coverage

insulin; diabetes; premixed insulin; biphasic insulin; human insulin; Type 2 DM; Type 1 DM; pregnancy-safe; hypoglycaemia-risk; NLEM India

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 (2018)

• AIIMS Endocrinology Protocols

• IAP Guidelines for Paediatric and Adolescent Diabetes

• WHO Model List of Essential Medicines (supportive)