Schedule H

Subcutaneous injection

• 100 units/mL solution for injection in 3 mL pre-filled pen (FlexPen/FlexTouch)

• 100 units/mL solution for injection in 10 mL vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Type 1 Diabetes Mellitus (T1DM)

Used as basal insulin component in basal-bolus regimen.

Parameter Recommendation

Starting dose 0.2–0.4 units/kg/day SC, administered once daily (evening/bedtime) or divided into twice daily

Titration Increase by 1–2 units every 3–4 days based on fasting plasma glucose (target: 80–130 mg/dL)

Usual maintenance dose 0.4–0.8 units/kg/day (as basal component; total daily insulin includes bolus)

Maximum dose No fixed upper limit; titrate based on glycaemic targets and clinical response

Clinical Notes:

• Once-daily dosing preferred; some patients require twice-daily dosing due to shorter duration compared to insulin glargine

• Must be used with rapid-acting/short-acting insulin for mealtime coverage

• Administer at consistent time each day

1. Type 2 Diabetes Mellitus (T2DM)

Used as basal insulin when oral hypoglycaemic agents fail to achieve glycaemic control, or as part of intensified insulin regimen.

Parameter Recommendation

Starting dose 10 units once daily SC at bedtime OR 0.1–0.2 units/kg/day

Titration Increase by 2–4 units once or twice weekly based on fasting glucose response

Usual maintenance dose 10–40 units/day (individualized based on glycaemic control)

Maximum dose No fixed maximum; titrate to achieve FBG and HbA1c targets

Clinical Notes:

• Can be continued alongside metformin and other oral agents

• Sulfonylurea dose reduction may be required to prevent hypoglycaemia

• Single daily dosing typically adequate in most T2DM patients

Secondary Indications — Adults (Off-label)

Indication Dose Notes

Gestational Diabetes Mellitus (GDM) requiring basal insulin Starting dose: 0.1–0.2 units/kg/day SC at bedtime; Titration: As per blood glucose monitoring OFF-LABEL — Specialist only. Based on international observational studies and limited Indian specialist practice. NPH insulin remains preferred first-line basal insulin in Indian obstetric guidelines. Use under maternal-fetal medicine or endocrinology supervision only.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Type 1 Diabetes Mellitus in Children (≥2 years)

Parameter Recommendation

Starting dose 0.2–0.4 units/kg/day SC once daily at bedtime

Titration Adjust by 10–15% of dose every 3–7 days based on SMBG and HbA1c; monitor closely for hypoglycaemia

Usual maintenance dose Basal component typically 40–50% of total daily insulin (0.5–1 units/kg/day as total)

Maximum dose No fixed limit; individualized to glycaemic targets

Clinical Notes:

• Twice-daily dosing may be required in children due to pharmacokinetic variability

• Regular SMBG essential; CGM if available

• Coordinate with rapid-acting insulin for meal coverage

Minimum Age: Approved for children ≥2 years of age. Use below 2 years is not recommended except under paediatric endocrinologist supervision in exceptional circumstances.

Secondary Indications — Paediatrics (Off-label)

Not applicable — No documented off-label paediatric indications per current Indian guidelines.

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

• During active hypoglycaemic episodes (defer administration until glucose normalized)

• Patients with irregular meal patterns or erratic carbohydrate intake — increased hypoglycaemia risk

• Renal or hepatic impairment — requires dose adjustments and close monitoring

• Elderly or underweight patients — heightened insulin sensitivity; start with lower doses

• When switching from other insulin types (NPH, glargine) — dose equivalence not exact; monitor closely during transition

• Hypokalemia risk — insulin promotes intracellular potassium shift

• Avoid intramuscular injection — unpredictable absorption

• Concurrent illness, stress, or infection — insulin requirements may increase

• Lipodystrophy at injection sites — rotate injection sites regularly

Parameter Recommendation

Safety Category Considered acceptable in pregnancy; extensive human data available

Preferred Alternatives NPH insulin remains the traditional first-choice basal insulin in Indian obstetric practice; insulin detemir is an acceptable alternative

When to Use May be used when basal insulin is required and NPH is not tolerated or when specialist preference dictates

Monitoring Frequent maternal blood glucose monitoring (SMBG); fetal growth surveillance via ultrasonography; standard obstetric monitoring

Parameter Recommendation

Breastfeeding Compatibility Compatible with breastfeeding

Drug Levels in Milk Expected to be minimal; insulin peptides degraded in infant GI tract

Preferred Alternatives No specific alternative needed; insulin detemir acceptable

Infant Monitoring Routine monitoring only; no specific concerns; ensure maternal glycaemic control to prevent feeding difficulties

Parameter Recommendation

Starting dose 0.1–0.2 units/kg/day or 10 units once daily; initiate at lower end of range

Titration Slower titration (every 5–7 days); conservative dose increments of 1–2 units

Additional Risks Hypoglycaemia (may be asymptomatic or atypical presentation); falls; cognitive impairment; underlying renal insufficiency; irregular meal intake; polypharmacy

Monitoring More frequent glucose monitoring; periodic renal function assessment; hypoglycaemia awareness evaluation

Interacting Drug/Class Mechanism/Effect Management

Beta-blockers (propranolol, atenolol) Mask hypoglycaemia symptoms (tachycardia, tremor); may prolong hypoglycaemia Avoid non-selective beta-blockers if possible; educate patient on alternative hypoglycaemia symptoms

Systemic corticosteroids Antagonize insulin action; induce hyperglycaemia Significant insulin dose increase often required; monitor glucose closely

Thiazolidinediones (pioglitazone) Additive fluid retention; increased heart failure risk when combined with insulin Monitor for oedema, weight gain, signs of CHF; avoid in patients with cardiac compromise

MAO inhibitors May enhance hypoglycaemic effect Monitor blood glucose; may need insulin dose reduction

Interacting Drug/Class Effect Management

Sulfonylureas (glimepiride, gliclazide) Additive hypoglycaemia risk Reduce sulfonylurea dose when initiating insulin; monitor glucose closely

ACE inhibitors May enhance insulin sensitivity Monitor for hypoglycaemia; dose adjustment may be needed

Fluoroquinolones (levofloxacin, moxifloxacin) Unpredictable glucose alterations (hypo- or hyperglycaemia) Enhanced glucose monitoring during antibiotic course

Thiazide and loop diuretics May worsen glycaemic control Monitor glucose; insulin dose increase may be required

Alcohol Potentiates and prolongs hypoglycaemia; impairs counter-regulatory response Counsel patient; avoid excessive alcohol intake

Salicylates (high dose) May enhance hypoglycaemic effect Monitor glucose if high-dose aspirin therapy initiated

Pentamidine Initial hypoglycaemia followed by hyperglycaemia possible Close glucose monitoring required

• Hypoglycaemia (most common; dose-related)

• Injection site reactions (pain, erythema, pruritus, swelling)

• Lipohypertrophy at injection sites

• Weight gain (less than with NPH insulin)

• Peripheral oedema (usually transient, early in therapy)

• Headache

Adverse Effect Clinical Significance

Severe hypoglycaemia May cause seizures, loss of consciousness, coma; requires immediate treatment; hospitalization may be needed

Anaphylaxis/severe hypersensitivity Rare; includes generalized urticaria, angioedema, bronchospasm, hypotension; discontinue immediately and treat as medical emergency

Severe lipodystrophy Can affect insulin absorption and glycaemic control; rotation of injection sites essential

Hypokalemia May occur with high insulin doses; monitor potassium, especially in patients on diuretics or with cardiac disease

Baseline:

• Fasting and postprandial blood glucose levels

• HbA1c

• Serum creatinine, eGFR

• Liver function tests

• Serum potassium (if indicated)

• Weight

After Initiation/Dose Change:

• Self-monitoring of blood glucose (SMBG): fasting glucose daily initially; pre-meal/bedtime as indicated

• Assess for hypoglycaemia symptoms

• Review injection technique and site rotation

Long-term:

• HbA1c every 3 months (or 6 months when stable)

• Renal function every 6–12 months

• Periodic hepatic function assessment

• Injection site examination for lipodystrophy

• Weight monitoring

• Hypoglycaemia frequency and awareness assessment

• Levemir® FlexPen (Novo Nordisk) — 3 mL pre-filled pen

• Levemir® Penfill (Novo Nordisk) — 3 mL cartridge

• Levemir® Vial (Novo Nordisk) — 10 mL vial

Note: No biosimilar versions currently available in Indian market.

• Not included in NLEM; not under NPPA price control

• Available in some state government diabetes control programmes

• May be provided free or subsidized at select tertiary care government hospitals

• Duration comparison: Insulin detemir has a flatter pharmacokinetic profile than NPH but shorter duration of action than insulin glargine U100; twice-daily dosing may be needed in 20–30% of patients

• Weight advantage: Associated with less weight gain compared to NPH insulin and insulin glargine — preferred in overweight/obese T2DM patients

• Pregnancy consideration: Among long-acting analogues, detemir has most pregnancy safety data; NPH remains first-line in most Indian obstetric settings

• Switching insulins: When switching from NPH, start detemir on unit-for-unit basis; when switching from glargine, may need 20–30% higher detemir dose

• Injection site matters: Rotate sites within same anatomic region (abdomen preferred for consistent absorption); inspect for lipohypertrophy at each visit

• Hypoglycaemia education: Counsel all patients and caregivers on recognition and management of hypoglycaemia, especially elderly and those on concurrent sulfonylureas

insulin detemir; long-acting insulin; basal insulin; type 1 diabetes; type 2 diabetes; Levemir; pregnancy-acceptable; renal-caution; hypoglycaemia; weight-neutral

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine

• ICMR Guidelines for Management of Type 2 Diabetes (2018)

• RSSDI Clinical Practice Recommendations for Management of Type 2 Diabetes

• AIIMS Antidiabetic Protocols

• IAP Guidelines on Childhood and Adolescent Diabetes

• Manufacturer product insert (Levemir® — Novo Nordisk)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics